Publications by authors named "Hyo Soo Kim"

592 Publications

Incidence and Predictors of Stent Thrombosis in Patients Treated with Stents for Coronary Bifurcation Narrowing (From the BIFURCAT Registry).

Am J Cardiol 2021 Jul 19. Epub 2021 Jul 19.

Division of Cardiology, Cardiovascular and Thoracic Department, University of Turin, Turin, Italy. Electronic address:

Percutaneous coronary interventions performed at coronary bifurcations yield high rates of stent thrombosis (ST). The aim of the present study was to investigate the predictors of ST in contemporary coronary bifurcation percutaneous coronary interventions. We retrospectively investigated the BIFURCAT (comBined Insights From the Unified RAIN and COBIS bifurcAtion regisTries) registry on coronary bifurcations to assess the incidence and predictors of definite ST, which were the study primary endpoints. Predictors of ST among patients on dual antiplatelet therapy (DAPT) were also examined. A total of 5330 patients were included. After a mean 2-years follow-up, 64 (1.2%) patients experienced ST. 42 (65.6%) ST patients were on DAPT. At multivariable analysis, age (HR 1.02, CI 1.01 to 1.05, p = 0,027), smoking status (HR 2.57, CI 1.49 to 4.44, p = 0.001), chronic kidney disease (HR 2.26, CI 1.24 to 4.12, p = 0.007) and a 2-stent strategy (HR 2.38, CI 1.37 to 4.14, p = 0.002) were independent predictors of ST, whereas intracoronary imaging (HR 0.42, CI 0.23 to 0.78, p = 0.006) and final kissing balloon (FKB) (HR 0.48, CI 0.29 to 0.82, p = 0.007) were protective against ST. Among patients on DAPT, smoking status and a 2-stent strategy significantly increased the risk of ST, while intracoronary imaging and FKB reduced the risk. In conclusion, age, smoking status, chronic kidney disease and a 2-stent strategy were significant predictors of ST, whereas intracoronary imaging use and FKB had a protective effect. Only smoking status and a 2-stent strategy significantly predicted ST in DAPT subgroup, while intracoronary imaging and FKB had a protective role.
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http://dx.doi.org/10.1016/j.amjcard.2021.06.031DOI Listing
July 2021

Differential Factors for Predicting Outcomes in Left Main versus Non-Left Main Coronary Bifurcation Stenting.

J Clin Med 2021 Jul 7;10(14). Epub 2021 Jul 7.

Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul 03080, Korea.

Background: No large-scale study has compared the clinical and angiographic predictors of cardiovascular events in patients with left main bifurcation (LMB) and non-LMB stenting after second-generation DES implantation. Herein, we investigated differential clinical and angiographic factors for predicting outcomes in LMB versus non-LMB stenting.

Methods: A total of 2648 patients with bifurcation lesions treated with second-generation DESs from the retrospective patient cohort were divided into an LMB group ( = 935) and a non-LMB group ( = 1713). The primary outcome was the 7-year incidence of target lesion failure (TLF), defined as the composite of cardiac death, myocardial infarction, and target lesion revascularization.

Results: The incidence of TLF was 9.8%. Those in the LMB group were associated with a higher risk of TLF (14.2% versus 7.5%, < 0.001) than those in the non-LMB group. Regarding the LMB group, independent predictors of TLF were chronic kidney disease (CKD), reduced left ventricular ejection fraction (LVEF), and two-stenting. Regarding the non-LMB group, CKD, reduced LVEF, old age, diabetes, and small diameter of the main vessel stent were independent predictors of TLF.

Conclusions: The two-stent strategy could potentially increase TLF for the LMB lesions, and achieving the maximal diameter of the main vessel stent could result in better clinical outcomes for non-LMB lesions.
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http://dx.doi.org/10.3390/jcm10143024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306985PMC
July 2021

Discovery of chemerin as the new chemoattractant of human mesenchymal stem cells.

Cell Biosci 2021 Jul 1;11(1):120. Epub 2021 Jul 1.

Molecular Medicine & Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine, Seoul National University, Seoul National University Hospital, 101 DeaHak-ro, JongRo-gu, Seoul, 03080, Republic of Korea.

Background: The homing capacity of human mesenchymal stem cells (hMSCs) to the injured sites enables systemic administration of hMSCs in clinical practice. In reality, only a small proportion of MSCs are detected in the target tissue, which is a major bottleneck for MSC-based therapies. We still don't know the mechanism how MSCs are chemo-attracted to certain target organ and engrafted through trans-endothelial migration. In this study, we aimed to determine the mechanism how the circulating hMSCs home to the injured liver.

Methods And Results: When we compare the cytokine array between normal and injured mouse liver at 1-day thioacetamide (TAA)-treatment, we found that chemerin, CXCL2, and CXCL10 were higher in the injured liver than normal one. Among three, only chemerin was the chemoattractant of hMSCs in 2D- and 3D-migration assay. Analysis of the signal transduction pathways in hMSCs showed that chemerin activated the phosphorylation of JNK1/2, ERK1/2 and p38, and finally upregulated CD44, ITGA4, and MMP-2 that are involved in the transendothelial migration and extravasation of MSCs. Upstream transcription regulators of CD44, ITGA4, and MMP-2 after chemerin treatment were MZF1, GATA3, STAT3, and STAT5A. To develop chemerin as a chemoattractant tool, we cloned gene encoding the active chemerin under the CMV promoter (CMV-aChemerin). We analyzed the migration of hMSCs in the 3D model for space of the Disse, which mimics transmigration of hMSCs in the liver. CMV-aChemerin-transfected hepatocytes were more effective to attract hMSC than control hepatocytes, leading to the enhanced transendothelial migration and homing of hMSCs to liver. The homing efficiency of the intravascularly-delivered hMSCs to liver was evaluated after systemic introduction of the CMV-aChemerin plasmid packed in liposome-vitamin A conjugates which target liver. CMV-aChemerin plasmid targeting liver significantly enhanced homing efficiency of hMSCs to liver compared with control plasmid vector.

Conclusions: Chemerin is the newly found chemoattractant of hMSCs and may be a useful tool to manipulate the homing of the intravascularly-administered hMSC to the specific target organ.
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http://dx.doi.org/10.1186/s13578-021-00631-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252297PMC
July 2021

Endothelin-1 enhances the regenerative capability of human bone marrow-derived mesenchymal stem cells in a sciatic nerve injury mouse model.

Biomaterials 2021 Jun 25;275:120980. Epub 2021 Jun 25.

Molecular Medicine & Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, College of Medicine, Seoul National University, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

We expanded the application of endothelin-1 (EDN1) by treating human mesenchymal stem cell (hMSC) organotypic spinal cord slice cultures with EDN1. EDN1-treated hMSCs significantly enhanced neuronal outgrowth. The underlying mechanism of this effect was evaluated via whole-genome methylation. EDN1 increased whole-genome demethylation and euchromatin. To observe demethylation downstream of EDN1, deaminases and glycosylases were screened, and APOBEC1 was found to cause global demethylation and OCT4 gene activation. The sequence of methyl-CpG-binding domain showed similar patterns between EDN1- and APOBEC1-induced demethylation. SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily A member 4 (SMARC A4) and SMARC subfamily D, member 2 (SMARC D2) were screened via methyl-CpG-binding domain sequencing as a modulator in response to EDN1. Chromatin immunoprecipitation of the H3K9me3, H3K27me3, and H3K4me4 binding sequences on the APOBEC1 promoter was analyzed following treatment with or without siSMARC A4 or siSMARC D2. The results suggested that SMARC A4 and SMARC D2 induced a transition from H3K9me3 to H3K4me3 in the APOBEC1 promoter region following EDN1 treatment. Correlations between EDN1 pathways and therapeutic efficacy in hBM-MSCs were determined in a sciatic nerve injury mouse model. Thus, EDN1 may be a useful novel-concept bioactive peptide and biomaterial component for improving hMSC regenerative capability.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120980DOI Listing
June 2021

Long-term outcomes after renal denervation in an Asian population: results from the Global SYMPLICITY Registry in South Korea (GSR Korea).

Hypertens Res 2021 Jun 18. Epub 2021 Jun 18.

Department of Internal Medicine, Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea.

The objective of this work was to investigate the long-term safety and efficacy of renal denervation in Korean patients from the Global SYMPLICITY Registry (GSR). GSR Korea is a substudy of GSR with additional inclusion and exclusion criteria compared to GSR, including inclusion criteria of office systolic blood pressure ≥160 mmHg, or ≥150 mmHg for type 2 diabetes patients, while receiving 3 or more antihypertensive medications without changes for 2 weeks prior to enrollment. Renal denervation was performed using a Symplicity Flex catheter for ablation in the main renal arteries. Changes in office systolic blood pressure and adverse events were collected for up to 36 months of follow-up for 102 patients in GSR Korea. In addition, adverse events and reductions in office systolic blood pressure were analyzed for patients with and without type II diabetes mellitus. Renal denervation led to mean (± standard deviation) reductions in office systolic blood pressure at 12, 24, and 36 months in GSR Korea (-26.7 ± 18.5, -30.1 ± 21.6 mmHg, and -32.5 ± 18.8, respectively). The proportion of patients with a ≥10 mmHg office systolic blood pressure reduction from baseline was 86.3% at 12 months, 86.5% at 24 months, and 89.7% at 36 months. Adverse events at 3 years were rare. In addition, reductions in office systolic blood pressure were similar for patients with vs. without diabetes mellitus (p > 0.05 at all timepoints). Office systolic blood pressure was safely reduced at up to 36 months post-renal denervation in GSR Korea, and adverse events were rare. In addition, patients with and without diabetes had similar office systolic blood pressure reductions.
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http://dx.doi.org/10.1038/s41440-021-00683-5DOI Listing
June 2021

Plant callus-derived shikimic acid regenerates human skin through converting human dermal fibroblasts into multipotent skin-derived precursor cells.

Stem Cell Res Ther 2021 06 11;12(1):346. Epub 2021 Jun 11.

Strategic Center of Cell and Bio Therapy for Heart, Diabetes & Cancer, Biomedical Research Institute, Seoul National University Hospital, Seoul, 03080, Republic of Korea.

Background: The human skin-derived precursors (SKPs) are a good cell source for regeneration. However, the isolation of SKP from human skin is limited. To overcome this drawback, we hypothesized that the component of plant stem cells could convert human fibroblasts to SKPs.

Methods: Human dermal fibroblasts were treated with shikimic acid, a major component of Sequoiadendron giganteum callus extract. The characteristics of these reprogrammed cells were analyzed by qPCR, western blot, colony-forming assay, and immunofluorescence staining. Artificial human skin was used for CO laser-induced wound experiments. Human tissues were analyzed by immunohistochemistry.

Results: The reprogrammed cells expressed nestin (a neural precursor-specific protein), fibronectin, and vimentin and could differentiate into the ectodermal and mesodermal lineage. Nestin expression was induced by shikimic acid through the mannose receptor and subsequent MYD88 activation, leading to P38 phosphorylation and then CREB binding to the nestin gene promoter. Finally, we confirmed that shikimic acid facilitated the healing of cut injury and enhanced dermal reconstruction in a human artificial skin model. Moreover, in a clinical study with healthy volunteers, plant callus extracts increased the expression of stem cell markers in the basal layer of the epidermis and collagen deposit in the dermis.

Conclusions: These results indicate that shikimic acid is an effective agent for tissue regeneration.
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http://dx.doi.org/10.1186/s13287-021-02409-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196440PMC
June 2021

Five-year clinical outcomes of the first Korean-made sirolimus-eluting coronary stent with abluminal biodegradable polymer.

Medicine (Baltimore) 2021 May;100(19):e25765

Department of Cardiology, Ajou University School of Medicine, Suwon.

Abstract: This study evaluated the 5-year clinical outcomes of the Genoss DES, the first Korean-made sirolimus-eluting coronary stent with abluminal biodegradable polymer.We previously conducted the first-in-patient prospective, multicenter, randomized trial with a 1:1 ratio of patients using the Genoss DES and Promus Element stents; the angiographic and clinical outcomes of the Genoss DES stent were comparable to those of the Promus Element stent. The primary endpoint was major adverse cardiac events (MACE), which was a composite of death, myocardial infarction (MI), and target lesion revascularization (TLR) at 5 years.We enrolled 38 patients in the Genoss DES group and 39 in the Promus Element group. Thirty-eight patients (100%) from the Genoss DES group and 38 (97.4%) from the Promus Element group were followed up at 5 years. The rates of MACE (5.3% vs 12.8%, P = .431), death (5.3% vs 10.3%, P = .675), TLR (2.6% vs 2.6%, P = 1.000), and target vessel revascularization (TVR) (7.9% vs 2.6%, P = .358) at 5 years did not differ significantly between the groups. No TLR or target vessel revascularization was reported from years 1 to 5 after the index procedure, and no MI or stent thrombosis occurred in either group during 5 years.The biodegradable polymer Genoss DES and durable polymer Promus Element stents showed comparable low rates of MACE at the 5-year clinical follow-up.
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http://dx.doi.org/10.1097/MD.0000000000025765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133141PMC
May 2021

Cardiovascular Outcomes Comparison of Dipeptidyl Peptidase-4 Inhibitors versus Sulfonylurea as Add-on Therapy for Type 2 Diabetes Mellitus: a Meta-Analysis.

J Lipid Atheroscler 2021 May 25;10(2):210-222. Epub 2021 Jan 25.

Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Objective: Recent studies have raised concern about the cardiovascular safety of dipeptidyl peptidase-4 (DPP4) inhibitors. We performed a systematic review through meta-analysis to compare cardiovascular outcomes of sulfonylurea (SU) versus DPP4 inhibitors when used in combination with metformin.

Methods: After searching for trials using combination therapy of metformin with DPP4 inhibitor or SU in PubMed, Cochrane Library, and Embase, one prospective observation study and 15 randomized controlled studies were selected.

Results: Regarding the primary analysis endpoint, there were no significant differences in the risk of all-cause mortality between SU and DPP4 inhibitors as an add-on therapy to metformin (random-effect relative risk [RR], 1.14; 95% confidence interval [CI], 0.98-1.33; =0.811; I=0%). Cardiovascular death was also similar between the two drug classes in the five studies which reported outcomes (random-effect RR, 1.03; 95% CI, 0.83-1.27; =0.517; I=0%). Furthermore, there were no significant differences in major adverse cardiac events (MACE), coronary heart disease, myocardial infarction, ischemic stroke and heart failure. However, there were less hypoglycemic events and weight gain in the DPP4 inhibitor group as compared with the SU group (random-effect RR, 3.79; 95% CI, 1.53-9.39; <0.001; I=98.2 and weighted mean difference, 1.68; 95% CI, 1.07-2.29; <0.001; I=94.7, respectively).

Conclusion: As add-on therapy to metformin, there were no significant differences in all-cause mortality and cardiovascular mortality between DPP4 inhibitors and SUs.
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http://dx.doi.org/10.12997/jla.2021.10.2.210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159755PMC
May 2021

HLA DR Genome Editing with TALENs in Human iPSCs Produced Immune-Tolerant Dendritic Cells.

Stem Cells Int 2021 20;2021:8873383. Epub 2021 May 20.

Strategic Center of Cell and Bio Therapy for Heart, Diabetes & Cancer, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea.

Although human induced pluripotent stem cells (iPSCs) can serve as a universal cell source for regenerative medicine, the use of iPSCs in clinical applications is limited by prohibitive costs and prolonged generation time. Moreover, allogeneic iPSC transplantation requires preclusion of mismatches between the donor and recipient human leukocyte antigen (HLA). We, therefore, generated universally compatible immune nonresponsive human iPSCs by gene editing. Transcription activator-like effector nucleases (TALENs) were designed for selective elimination of HLA DR expression. The engineered nucleases completely disrupted the expression of HLA DR on human dermal fibroblast cells (HDF) that did not express HLA DR even after stimulation with IFN-. Teratomas formed by HLA DR knockout iPSCs did not express HLA DR, and dendritic cells differentiated from HLA DR knockout iPSCs reduced CD4 T cell activation. These engineered iPSCs might provide a novel translational approach to treat multiple recipients from a limited number of cell donors.
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http://dx.doi.org/10.1155/2021/8873383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163544PMC
May 2021

Comparison of 2-Stenting Strategies Depending on Sequence or Technique for Bifurcation Lesions in the Second-Generation Drug-Eluting Stent Era - Analysis From the COBIS (Coronary Bifurcation Stenting) III Registry.

Circ J 2021 Jun 2. Epub 2021 Jun 2.

Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital.

Background: It has not been determined which specific 2-stenting strategy is the best for bifurcation lesions. Our aim was to investigate the clinical outcomes of various 2-stenting strategies in the era of 2nd-generation drug-eluting stents (2G-DES).Methods and Results:We analyzed 454 patients who finally underwent 2-stenting for a bifurcation lesion, from among 2,648 patients enrolled in the COBIS III registry. The primary outcome was target lesion failure (TLF). Patients were analyzed according to stenting sequence (provisional [main vessel stenting first] vs. systemic [side branch stenting first]) and stenting technique (crush vs. T vs. culotte vs. kissing/V stenting). Overall, 4.4 years' TLF after 2-stenting treatment for bifurcation lesion was excellent: TLF 11.2% and stent thrombosis 1.3%. There was no difference in TLF according to 2-stenting strategy (11.1% vs. 10.5%, P=0.990 for provisional and systemic sequence; 8.6% vs. 14.4% vs. 12.9% vs. 12.2%, P=0.326 for crush, T, culotte, kissing/V technique, respectively). Only left main (LM) disease and a shorter duration of dual antiplatelet therapy (DAPT) were associated with TLF. The distribution of DAPT duration differed between patients with and without TLF, and the time-point of intersection was 2.5 years. Also, the side branch was the most common site of restenosis.

Conclusions: The stenting sequence or technique did not affect clinical outcomes, but LM disease and shorter DAPT were associated with TLF, in patients with bifurcation lesions undergoing 2-stenting with 2G-DES.
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http://dx.doi.org/10.1253/circj.CJ-20-0999DOI Listing
June 2021

Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention (HOST-EXAM): an investigator-initiated, prospective, randomised, open-label, multicentre trial.

Lancet 2021 Jun 16;397(10293):2487-2496. Epub 2021 May 16.

Department of Internal Medicine, Cardiology Centre, Seoul National University Hospital, Seoul, South Korea. Electronic address:

Background: Optimal antiplatelet monotherapy during the chronic maintenance period in patients who undergo coronary stenting is unknown. We aimed to compare head to head the efficacy and safety of aspirin and clopidogrel monotherapy in this population.

Methods: We did an investigator-initiated, prospective, randomised, open-label, multicentre trial at 37 study sites in South Korea. We enrolled patients aged at least 20 years who maintained dual antiplatelet therapy without clinical events for 6-18 months after percutaneous coronary intervention with drug-eluting stents (DES). We excluded patients with any ischaemic and major bleeding complications. Patients were randomly assigned (1:1) to receive a monotherapy agent of clopidogrel 75 mg once daily or aspirin 100 mg once daily for 24 months. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium (BARC) bleeding type 3 or greater, in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02044250.

Findings: Between March 26, 2014, and May 29, 2018, we enrolled 5530 patients. 5438 (98·3%) patients were randomly assigned to either the clopidogrel group (2710 [49·8%]) or to the aspirin group (2728 [50·2%]). Ascertainment of the primary endpoint was completed in 5338 (98·2%) patients. During 24-month follow-up, the primary outcome occurred in 152 (5·7%) patients in the clopidogrel group and 207 (7·7%) in the aspirin group (hazard ratio 0·73 [95% CI 0·59-0·90]; p=0·0035).

Interpretation: Clopidogrel monotherapy, compared with aspirin monotherapy during the chronic maintenance period after percutaneous coronary intervention with DES significantly reduced the risk of the composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and BARC bleeding type 3 or greater. In patients requiring indefinite antiplatelet monotherapy after percutaneous coronary intervention, clopidogrel monotherapy was superior to aspirin monotherapy in preventing future adverse clinical events.

Funding: ChongKunDang, SamJin, HanMi, DaeWoong, and the South Korea Ministry of Health and Welfare.
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http://dx.doi.org/10.1016/S0140-6736(21)01063-1DOI Listing
June 2021

Immediate Compared With Delayed Percutaneous Coronary Intervention for Patients With ST-Segment-Elevation Myocardial Infarction Presenting ≥12 Hours After Symptom Onset Is Not Associated With Improved Clinical Outcome.

Circ Cardiovasc Interv 2021 May 18;14(5):e009863. Epub 2021 May 18.

Cardiovascular Center, Seoul National University Hospital, Seoul, Republic of Korea (Y.-J.K., J.K., H.-M.Y., K.W.P., H.-J.K., B.-K.K., J.-K.H., H.-S.K.).

[Figure: see text].
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.009863DOI Listing
May 2021

De-escalation of Prasugrel Results in Higher Percentage of Patients within Optimal Range of Platelet Reactivity: Analysis from the HOST-REDUCE-POLYTECH-ACS Trial.

Thromb Haemost 2021 Apr 30. Epub 2021 Apr 30.

Department of Internal Medicine, Cardiovascular Center, Seoul National University Hospital, Seoul, Republic of Korea.

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http://dx.doi.org/10.1055/a-1496-7987DOI Listing
April 2021

Left Ventricular Ejection Fraction 1 Year After Acute Myocardial Infarction Identifies the Benefits of the Long-Term Use of β-Blockers: Analysis of Data From the KAMIR-NIH Registry.

Circ Cardiovasc Interv 2021 Apr 20;14(4):e010159. Epub 2021 Apr 20.

Department of Internal Medicine, Seoul National University Hospital, Republic of Korea (C.S.P., H.-M.Y., Y.-J.K., J.K., J.-K.H., K.W.P., H.-J.K., B.-K.K., H.-S.K.).

[Figure: see text].
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.010159DOI Listing
April 2021

Direct conversion of adult human fibroblasts into functional endothelial cells using defined factors.

Biomaterials 2021 05 24;272:120781. Epub 2021 Mar 24.

Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea. Electronic address:

We aimed to directly convert adult human dermal fibroblasts (aHDFs) into functional endothelial cells (ECs). Lentiviral vectors encoding endothelial transcription factors (TFs) were constructed. We examined whether five TFs (FOXO1, ER71, KLF2, TAL1, and LMO2) used for the generation of mouse induced ECs (iECs) could convert the aHDFs into human iECs. Twenty-eight days after transduction with lentiviral constructs, 32.1 ± 5.1% cells expressed vascular endothelial (VE)-cadherin. Factor screening revealed that only three factors (3F: ER71, KLF2, and TAL1) were necessary to induce VE-cadherin (+) cells (49.4 ± 3.5%). However, whole transcriptome sequencing showed that VE-cadherin (+) cells were not completely reprogrammed. Mature iECs double-positive for VE-cadherin/Pecam1 (DP cells) with a cobblestone appearance were obtained at a frequency of only 5.1 ± 0.6%. Using whole transcriptome analysis, the potential factors that could block the conversion were screened. Among candidates TWIST1-knockdown enhanced efficiency of conversion. Rosiglitazone, an inhibitor of epithelial-mesenchymal transition (EMT), also improved the conversion efficiency. Moreover, a 2nd second-stage conversion process, in which VE-cadherin (+) cells were incubated for additional two weeks, further enhanced the efficiency. The final protocol for 6 weeks yielded a conversion rate of 19.6 ± 3.0% iECs, defined by DP cells depicting the nature of mature ECs in various analyses. Further analyses revealed that the genetic and epigenetic profiles of iECs resembled those of functional ECs. Collectively, aHDFs can be converted into functional ECs through the transduction of ER71, KLF2, and TAL1, combined with two EMT inhibitors (siTWIST1 and rosiglitazone), followed by 2nd stage conversion.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120781DOI Listing
May 2021

2021 Korean Society of Myocardial Infarction Expert Consensus Document on Revascularization for Acute Myocardial Infarction.

Korean Circ J 2021 Apr;51(4):289-307

Department of Cardiovascular Medicine, Chonnam National University Hospital, Gwangju, Korea.

Acute myocardial infarction (AMI) is a fatal manifestation of ischemic heart disease and remains a major public health concern worldwide despite advances in its diagnosis and management. The characteristics of patients with AMI, as well as its disease patterns, have gradually changed over time in Korea, and the outcomes of revascularization have improved dramatically. Several characteristics associated with the revascularization of Korean patients differ from those of patients in other countries. The sophisticated state of AMI revascularization in Korea has led to the need for a Korean expert consensus. The Task Force on Expert Consensus Document of the Korean Society of Myocardial Infarction has comprehensively reviewed the outcomes of large clinical trials and current practical guidelines, as well as studies on Korean patients with AMI. Based on these comprehensive reviews, the members of the task force summarize the major guidelines and recent publications, and propose an expert consensus for revascularization in patients with AMI.
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http://dx.doi.org/10.4070/kcj.2021.0043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022023PMC
April 2021

The validation of the dual antiplatelet therapy score in East Asians receiving percutaneous coronary intervention with exclusively second generation drug-eluting stents.

Catheter Cardiovasc Interv 2021 Apr 5. Epub 2021 Apr 5.

Cardiovascular Center, Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.

Objectives: We investigated whether the dual antiplatelet therapy (DAPT) score (DS) predicts clinical outcome in an East-Asian population that received exclusively second generation drug-eluting stent (DES).

Backgrounds: It is uncertain whether the DS could adequately risk stratify patients exclusively receiving second generation DES.

Methods: From the Grand-DES registry, we evaluated patients who were treated with DAPT for at least 12 months and were event-free at 12 months after DES implantation. Patients were classified into two categories: high DS (≧2) (n = 3,157); and low DS (<2) (n = 5,226). The primary ischemic outcome was a composite of stent thrombosis and all myocardial infarction (MI), and the primary bleeding outcome was TIMI major or minor bleeding. A propensity score (PS)-matched analysis was done to correct for baseline differences between extended DAPT group and the conventional group.

Results: Among 8,383 subjects, the primary ischemic outcome occurred in 48 patients (0.6%) and the primary bleeding outcome in 49 patients (0.6%). High DS was associated with a higher incidence of ischemic events (ischemic outcome: 0.8% vs. 0.4%, for high vs. low DS, Log-rank p = .039), but not with any differences in bleeding events (Log-rank p = .734). In the PS-matched analysis, extended group was associated with lower risk of composite endpoint of MI, stent thrombosis, or cardiac death in only the high DS group (1.8% vs. 3.7%, Log-rank p = .004; hazard ratio 0.45, 95% confidence interval 0.27-0.76; p = .003 after adjustment).

Conclusions: The DS was an adequate risk stratifier for future ischemic events in East Asians receiving exclusively second generation DES.
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http://dx.doi.org/10.1002/ccd.29682DOI Listing
April 2021

Adhesion GPCR Latrophilin-2 Specifies Cardiac Lineage Commitment through CDK5, Src, and P38MAPK.

Stem Cell Reports 2021 Apr 1;16(4):868-882. Epub 2021 Apr 1.

Strategic Center of Cell & Bio Therapy, Seoul National University Hospital, Seoul 03080, Republic of Korea; Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea; Program in Stem Cell Biology, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

Identifying lineage-specific markers is pivotal for understanding developmental processes and developing cell therapies. Here, we investigated the functioning of a cardiomyogenic cell-surface marker, latrophilin-2 (LPHN2), an adhesion G-protein-coupled receptor, in cardiac differentiation. LPHN2 was selectively expressed in cardiac progenitor cells (CPCs) and cardiomyocytes (CMCs) during mouse and human pluripotent stem cell (PSC) differentiation; cell sorting with an anti-LPHN2 antibody promoted the isolation of populations highly enriched in CPCs and CMCs. Lphn2 knockdown or knockout PSCs did not express cardiac genes. We used the Phospho Explorer Antibody Array, which encompasses nearly all known signaling pathways, to assess molecular mechanisms underlying LPHN2-induced cardiac differentiation. LPHN2-dependent phosphorylation was the strongest for cyclin-dependent kinase 5 (CDK5) at Tyr15. We identified CDK5, Src, and P38MAPK as key downstream molecules of LPHN2 signaling. These findings provide a valuable strategy for isolating CPCs and CMCs from PSCs and insights into the still-unknown cardiac differentiation mechanisms.
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http://dx.doi.org/10.1016/j.stemcr.2021.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072181PMC
April 2021

Derivation and validation of a combined in-hospital mortality and bleeding risk model in acute myocardial infarction.

Int J Cardiol Heart Vasc 2021 Apr 22;33:100732. Epub 2021 Feb 22.

Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea.

Background: In the potent new antiplatelet era, it is important issue how to balance the ischemic risk and the bleeding risk. However, previous risk models have been developed separately for in-hospital mortality and major bleeding risk. Therefore, we aimed to develop and validate a novel combined model to predict the combined risk of in-hospital mortality and major bleeding at the same time for initial decision making in patients with acute myocardial infarction (AMI).

Methods: Variables from the Korean Acute Myocardial Infarction Registry (KAMIR) - National Institute of Health (NIH) database were used to derive (n = 8955) and validate (n = 3838) a multivariate logistic regression model. Major adverse cardiovascular events (MACEs) were defined as in-hospital death and major bleeding.

Results: Seven factors were associated with MACE in the model: age, Killip class, systolic blood pressure, heart rate, serum glucose, glomerular filtration rate, and initial diagnosis. The risk model discriminated well in the derivation (c-static = 0.80) and validation (c-static = 0.80) cohorts. The KAMIR-NIH risk score was developed from the model and corresponded well with observed MACEs: very low risk (0.9%), low risk (1.7%), moderate risk (4.2%), high risk (8.6%), and very high risk (23.3%). In patients with MACEs, a KAMIR-NIH risk score ≤ 10 was associated with high bleeding risk, whereas a KAMIR-NIH risk score > 10 was associated with high in-hospital mortality.

Conclusion: The KAMIR-NIH in-hospital MACEs model using baseline variables stratifies comprehensive risk for in-hospital mortality and major bleeding, and is useful for guiding initial decision making.
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http://dx.doi.org/10.1016/j.ijcha.2021.100732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907424PMC
April 2021

Sex-related impact on clinical outcomes of patients treated with drug-eluting stents according to clinical presentation: Patient-level pooled analysis from the GRAND-DES registry.

Cardiol J 2021 Feb 26. Epub 2021 Feb 26.

Cardiovascular Center, Seoul National University Hospital, Seoul, Republic of Korea.

Background: The contribution of sex and initial clinical presentation to the long-term outcomes in patients undergoing percutaneous coronary intervention (PCI) is still debated.

Methods: Individual patient data from 5 Korean-multicenter drug-eluting stent (DES) registries (The GRAND-DES) were pooled. A total of 17,286 patients completed 3-year follow-up (5216 women and 12,070 men). The median follow-up duration was 1125 days (interquartile range 1097-1140 days), and the primary endpoint was cardiac death at 3 years.

Results: The clinical indication for PCI was stable angina pectoris (SAP) in 36.8%, unstable angina pectoris (UAP) or non-ST-segment elevation myocardial infarction (NSTEMI) in 47.4%, and STEMI in 15.8%. In all groups, women were older and had a higher proportion of hypertension and diabetes mellitus compared with men. Women presenting with STEMI were older than women with SAP, with the opposite seen in men. There was no sex difference in cardiac death for SAP or UAP/NSTEMI. In STEMI patients, the incidence of cardiac death (7.9% vs. 4.4%, p = 0.001), all-cause mortality (11.1% vs. 6.9%, p = 0.001), and minor bleeding (2.2% vs. 1.2%, p = 0.043) was significantly higher in women. After multivariable adjustment, cardiac death was lower in women for UAP/NSTEMI (HR 0.69, 95% CI 0.53-0.89, p = 0.005), while it was similar for STEMI (HR 0.97, 95% CI 0.65-1.44, p = 0.884).

Conclusions: There was no sex difference in cardiac death after PCI with DES for SAP and UAP/NSTEMI patients. In STEMI patients, women had worse outcomes compared with men; however, after the adjustment of confounders, female sex was not an independent predictor of mortality.
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http://dx.doi.org/10.5603/CJ.a2021.0008DOI Listing
February 2021

Coronary vasospasm-induced syncope with dynamic changes of regional wall motion abnormalities confirmed real-time: a case report.

Eur Heart J Case Rep 2020 Dec 8;4(6):1-5. Epub 2020 Nov 8.

Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, 101 Daehang-ro, Chongno-gu, Seoul110-744, Republic of Korea.

Background: Coronary vasospasm is primarily characterized by transient and reversible vasoconstriction causing myocardial ischaemia and can manifest with various clinical features, including syncope.

Case Summary: A 50-year-old man presented with recurrent episodes of syncope for 3 days. The last syncope history occurred during an early morning walk, accompanied by dizziness and loss of consciousness. There was no clear history of chest pain at the time. He smoked one pack of cigarettes daily and frequently consume alcohol. Approximately 3 h after admission, echocardiography initially revealed normal systolic function; however, during the examination, the patient suddenly complained of dizziness and regional wall motion abnormalities (RWMA) of the left anterior descending artery (LAD) territory were observed. Both RWMA and dizziness spontaneously improved within a few minutes. Emergency coronary angiography (CAG) was performed to confirm vasospasm. Coronary angiography revealed mild atherosclerosis of proximal LAD. After 3 min, he complained of dizziness and vague chest discomfort, and electrocardiogram revealed ST-segment elevation. We immediately performed angiography of the left coronary artery, and CAG revealed total occlusion of the proximal LAD without any provocation. After administration of intracoronary nitroglycerine, coronary flow was restored completely and ST-segment deviation normalized along with relief in chest discomfort. The patient's symptoms have not recurred for 3 months while being on calcium channel blocker and long-acting nitrates.

Discussion: Coronary vasospasm can present as transient and dynamic myocardial ischaemia along with angina. Coronary vasospasm should always be considered in the differential diagnosis for syncope.
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http://dx.doi.org/10.1093/ehjcr/ytaa237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891269PMC
December 2020

Relative Impact of Clinical Risk Versus Procedural Risk on Clinical Outcomes After Percutaneous Coronary Intervention.

Circ Cardiovasc Interv 2021 02 5;14(2):e009642. Epub 2021 Feb 5.

Department of Internal Medicine and Cardiovascular Centre, Seoul National University Hospital, Korea.

Background: The clinical outcome after percutaneous coronary intervention (PCI) is affected by various clinical and procedural risk factors. We investigated the relative impact of clinical and procedural risks on clinical outcomes after PCI.

Methods: A total of 13 172 patients were enrolled from the Grand-DES registry. The population was grouped into tertiles (high-, intermediate-, low-risk) according to the number of prespecified clinical and procedural risk factors, respectively. The primary end point was major adverse cardiac and cerebrovascular events (MACCE) at 3 years post-PCI.

Results: MACCE occurred in 1109 (8.4%) patients during the follow-up period (median duration: 1126 days). Compared with procedural risk, clinical risk showed superior predictive power (area under the curve: 0.678 versus 0.570, <0.001, for clinical and procedural risks, respectively) and greater magnitude of effect in the multivariate analysis for MACCE (Clinical risk: hazard ratio, 1.953 [95% CI, 1.809-2.109], <0.001; procedural risk: hazard ratio, 1.240 [95% CI, 1.154-1.331], <0.001). In subgroup analyses within each clinical risk tertile, procedural risk had no significant impact on MACCE in the lowest clinical risk tertile. An annual landmark analysis revealed that clinical and procedural risks were both significant predictors of MACCE, which occurred within the first and second year post-PCI. However, for MACCE occurring in the third year post-PCI, only clinical risk but not procedural risk was a significant predictor of events.

Conclusions: Clinical and procedural risks were both significant predictors for ischemic clinical events in patients undergoing PCI. However, clinical risk had a greater and more prolonged effect on outcomes than procedural risk. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03507205.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.009642DOI Listing
February 2021

Procedural optimization of drug-coated balloons in the treatment of coronary artery disease.

Catheter Cardiovasc Interv 2021 Jul 25;98(1):E43-E52. Epub 2021 Jan 25.

Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul, Republic of Korea.

Objectives: This study aimed to investigate the effects of procedural optimization on the clinical outcomes of using the drug-coated balloon (DCB) in the treatment of coronary artery disease.

Backgrounds: Procedural optimization is considered an essential step in DCB treatment.

Methods: Data of consecutive patients who underwent DCB treatment at the Seoul National University Hospital were collected. The primary outcome was target lesion failure (TLF) at 2 years.

Results: Among 259 patients (309 lesions), TLF was observed in 31 (12.0%) patients. The following were modifiable procedural factors: residual percent diameter stenosis (%DS) after lesion preparation; DCB-to-vessel/stent ratio; time-delay to inflation; and total DCB inflation time. The best cutoff values for these parameters were 20%, 0.95, 25, and 60 s, respectively. The patients were classified based on the number of procedural factors that satisfied adequate criteria. TLF was observed in 7.3% in the fully optimized group, 9.1% in the partially optimized group, and 34.1% in the nonoptimized group over 2 years (p < .001). The adequacy of the four factors for DCB optimization was an independent predictor of TLF (adjusted hazards ratio for each unmet criteria for optimization, 2.05, 95% confidence interval 1.74-2.36, p < .001).

Conclusion: The optimization of the four procedural factors could reduce TLF following DCB treatment.
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http://dx.doi.org/10.1002/ccd.29492DOI Listing
July 2021

Association of Side-Branch Treatment and Patient Factors in Left Anterior Descending Artery True Bifurcation Lesions: Analysis from the GRAND-DES Pooled Registry.

J Interv Cardiol 2020 27;2020:8858642. Epub 2020 Dec 27.

Department of Internal Medicine, Cardiovascular Center, Seoul National University Hospital, Seoul 03080, Republic of Korea.

Methods: Patients undergoing PCI to left anterior descending (LAD) bifurcation lesions with contemporary DES were analyzed from a nationwide registry. Baseline risk was assessed using the Age, Creatinine, and Ejection Fraction (ACEF) score. Target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction, and target lesion revascularization, was assessed at 3 years.

Results: Among 1,089 patients with LAD bifurcation lesions, 548 (50.3%) patients underwent SB treatment. The SB treatment group showed a nonsignificant, but numerically lower rate of 3-year TLF (6.6% vs. 9.2%, HR 0.75, 95%CI 0.44-1.28,  = 0.29). In patients with low pretreatment risk (ACEF<1.22), SB treatment was associated with a lower rate of 3-year TLF (HR 0.43, 95%CI 0.19-0.96,  = 0.04), while no significant difference was observed in patients with high risk (ACEF≥1.22). The difference in the low risk group was mostly driven by target lesion revascularization (HR 0.24, 95%CI 0.08-0.75,  = 0.01).

Conclusions: SB treatment for LAD bifurcation lesions showed favorable long-term outcomes compared with main-branch-only intervention, especially in patients with low pretreatment risk.
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http://dx.doi.org/10.1155/2020/8858642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781708PMC
May 2021

Percutaneous treatment of unprotected left main disease with thin strut durable polymer or early-generation thicker strutted and coated bioabsorbable polymer drug-eluting stents in a large-scale registry.

Cardiovasc Revasc Med 2020 Dec 31. Epub 2020 Dec 31.

Cardiovascular Center, Seoul National University Hospital, Seoul, Republic of Korea.

Background: The ideal drug-eluting stent (DES) for the treatment of unprotected left main coronary artery (ULMCA) is unknown. We compared percutaneous coronary intervention (PCI) using durable polymers versus early-generation, thicker strutted and coated bioabsorbable polymers for ULMCA disease.

Methods: Patients who underwent ULMCA PCI (893 patients) from April 2008 to November 2014 were identified from the Grand-DES registry. The primary end point was 3-year target lesion failure (TLF) after propensity score matching.

Results: The final analysis included 754 patients (84.4%) and 139 patients (15.6%) in the durable and bioabsorbable polymer group, respectively. The groups differed significantly in lesion and procedural characteristics. Propensity score-matched analysis revealed a trend toward a lower 3-year TLF in the durable polymer group (log rank p=0.071). Independent predictors of 3-year TLF were chronic kidney disease, presentation with acute myocardial infarction, and a two-stenting technique for ULMCA lesions. Definite/probable stent thrombosis rates at 3-years were low in both groups (0.8% vs. 0.7%, p=0.925).

Conclusions: The safety of ULCMA PCI was excellent, and durable and bioabsorbable polymer DES provided similar clinical outcomes at 3-year follow-up. Landmark analysis revealed that the durable polymer group had a lower TLF rate from 9 months. Further studies are needed to confirm these results.
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http://dx.doi.org/10.1016/j.carrev.2020.12.034DOI Listing
December 2020

Sex differences in patients undergoing transcatheter aortic valve replacement in Asia.

Open Heart 2021 01;8(1)

Department of Cardiology, Sichuan University West China Hospital, Chengdu, China.

Objectives: Transcatheter aortic valve replacement (TAVR) is increasingly performed. Physically small Asians have smaller aortic root and peripheral vessel anatomy. The influence of gender of Asian patients undergoing TAVR is unknown and may affect outcomes. The aim of this study was to assess sex differences in Asian patients undergoing TAVR.

Methods: Patients undergoing TAVR from eight countries were enrolled. In this retrospective analysis, we examined differences in characteristics, 30-day clinical outcomes and 1-year survival between female and male Asian patients.

Results: Eight hundred and seventy-three patients (54.4% women) were included. Women were older, smaller and had less coronary artery and lung disease but tended to have higher logistic EuroSCOREs. Smaller prostheses were used more often in women. Major vascular complications occurred more frequently in women (5.5% vs 1.8%, p<0.01); however, 30-day stroke and mortality (women vs men: 1.5% vs 1.6%, p=0.95% and 4.3% vs 3.4%, p=0.48) were similar. Functional status improvement was significant and comparable between the sexes. Conduction disturbance and permanent pacemaker requirements (11.2% vs 9.0%, p=0.52) were also similar as was 1-year survival (women vs men: 85.6% vs 88.2%, p=0.25). The only predictors of 30-day mortality were major vascular injury in women and age in men.

Conclusions: Asian women had significantly smaller stature and anatomy with some differences in clinical profiles. Despite more frequent major vascular complications, women had similar 30-day stroke or mortality rates. Functional status improvement was significant and comparable between the sexes. Conduction disturbance and permanent pacemaker requirements were similar as was 1-year survival.
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http://dx.doi.org/10.1136/openhrt-2020-001541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798412PMC
January 2021

Effects of Asian dust-derived particulate matter on ST-elevation myocardial infarction: retrospective, time series study.

BMC Public Health 2021 01 7;21(1):68. Epub 2021 Jan 7.

Institute of Health and Environment, Seoul National University, Gwanak-ro, Seoul, 08826, Republic of Korea.

Background: Dust storms affect human health by impairing visibility and promoting interactions with microscopic organisms, such as bacteria and fungi. Although ST-elevation MI (STEMI) and non-ST-elevation MI (NSTEMI) differ mechanistically, few studies have investigated the incidence of cardiovascular diseases according to infarction type; these studies have yielded inconsistent findings. This study aimed to examine whether PM size (< 2.5 μm (PM) and < 10 μm (PM)) modifies the effect of Asian dust on acute myocardial infarction (AMI), with separate analyses for STEMI and NSTEMI.

Methods: MI-related data from 9934 emergency visits were collected from the Korea AMI Registry from 2005 to 2017. Asian dust events were defined as days with visibility of ≤10 km. Generalized linear models were used to analyze data with natural cubic splines. To examine potential modifiers, analyses were stratified by age, smoking status, and body mass index (BMI).

Results: No significant associations were observed between Asian dust and AMI. By adjusting for different lag structures, a significant effect was exclusively observed in STEMI. For moving average lags, the largest value at lag 5 (relative risk [RR] 1.083; 95% confidence interval [CI], 1.007-1.166) for single and lags 0-7 (RR 1.067; 95% CI: 1.002-1.136) was observed for PM; for PM, the largest significant effect was observed at lag 4 (RR 1.075; 95% CI: 1.010-1.144) for single and lags 0-7 (RR 1.067; 95% CI: 1.002-1.136). RRs were significantly higher in < 65-year-olds than in ≥65-year-olds. Additionally, RRs between the BMI < 25 and BMI ≥ 25 groups were not different; statistically significant effects were observed for concentration at lags 0-5 (RR: 1.073; 95% CI: 1.002-1.150) and lags 0-6 (RR: 1.071; 95% CI: 1.001-1.146) in the BMI < 25 group. A negative exposure-response association was observed between daily average visibility-adjusted PM and STEMI and daily average visibility-adjusted PM in < 65-year-olds.

Conclusions: Reducing PM and PM emissions, particularly during the days of Asian dust, may be crucial and reduce STEMI and AMI incidence among < 65-year-olds. These results indicate that the Asian dust alarm system needs revision to protect vulnerable populations.
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http://dx.doi.org/10.1186/s12889-020-10067-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791846PMC
January 2021

Retinol from hepatic stellate cells via STRA6 induces lipogenesis on hepatocytes during fibrosis.

Cell Biosci 2021 Jan 6;11(1). Epub 2021 Jan 6.

Molecular Medicine & Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine, Seoul National University, Seoul, Republic of Korea.

Background: Hepatic stellate cells (HSCs) are activated in response to liver injury with TIF1γ-suppression, leading to liver fibrosis. Here, we examined the mechanism how reduction of TIF1γ in HSCs induces damage on hepatocytes and liver fibrosis.

Method: Lrat:Cas9-ERT2:sgTif1γ mice were treated Tamoxifen (TMX) or wild-type mice were treated Thioacetamide (TAA). HSCs were isolated from mice liver and analyzed role of Tif1γ. HepG2 were treated retinol with/without siRNA for Stimulated by retinoic acid 6 (STRA6) or Retinoic acid receptor(RAR)-antagonist, and LX2 were treated siTIF1γ and/or siSTRA6. TAA treated mice were used for evaluation of siSTRA6 effect in liver fibrosis.

Results: When we blocked the Tif1γ in HSCs using Lrat:Cas9-ERT2:sgTif1γ mice, retinol is distributed into hepatocytes. Retinol influx was confirmed using HepG2, and the increased intracellular retinol led to the upregulation of lipogenesis-related-genes and triglyceride. This effect was inhibited by a RAR-antagonist or knock-down of STRA6. In the LX2, TIF1γ-suppression resulted in upregulation of STRA6 and retinol release, which was inhibited by STRA6 knock-down. The role of STRA6-mediated retinol transfer from HSCs to hepatocytes in liver fibrosis was demonstrated by in vivo experiments where blocking of STRA6 reduced fibrosis.

Conclusions: Retinol from HSCs via STRA6 in response to injury with TIF1γ-reduction is taken up by hepatocytes via STRA6, leading to fat-deposition and damage, and liver fibrosis.
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http://dx.doi.org/10.1186/s13578-020-00509-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789180PMC
January 2021

Association Between Low Muscle Mass and Prognosis of Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention.

J Am Heart Assoc 2021 01 29;10(1):e018554. Epub 2020 Dec 29.

Department of Internal Medicine and Cardiovascular Center Seoul National University Hospital Seoul Republic of Korea.

Background Low muscle mass has been associated with poor prognosis in certain chronic diseases, but its clinical significance in patients with coronary artery disease is unclear. We assessed the clinical significance of 2 easily measured surrogate markers of low muscle mass: the ratio of serum creatinine to serum cystatin C (Scr/Scys), and the ratio of estimated glomerular filtration rate by Scys to Scr (eGFRcys/eGFRcr). Methods and Results Patients with coronary artery disease undergoing percutaneous coronary intervention were prospectively enrolled from a single tertiary center, and Scr and Scys levels were simultaneously measured at admission. Best cut-off values for Scr/Scys and eGFRcys/eGFRcr to discriminate 3-year mortality were determined; 1.0 for men and 0.8 for women in Scr/Scys, and 1.1 for men and 1.0 for women in eGFRcys/eGFRcr. The prognostic values on 3-year mortality and the additive values of 2 markers on the predictive model were compared. In 1928 patients enrolled (mean age 65.2±9.9 years, 70.8% men), the risk of 3-year mortality increased proportionally according to the decrease of the surrogate markers. Both Scr/Scys- and eGFRcys/eGFRcr-based low muscle mass groups showed significantly higher risk of death, after adjusting for possible confounders. They also increased predictive power of the mortality prediction model. Low Scr/Scys values were associated with high mortality rate in patients who were ≥65 years, nonobese, male, had renal dysfunction at baseline, and presented with acute myocardial infarction. Conclusions Serum surrogate markers of muscle mass, Scr/Scys, and eGFRcys/eGFRcr may have clinical significance for detecting patients with coronary artery disease at high risk for long-term mortality.
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http://dx.doi.org/10.1161/JAHA.120.018554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955465PMC
January 2021

Gender differences in clinical outcomes of acute myocardial infarction undergoing percutaneous coronary intervention: insights from the KAMIR-NIH Registry.

J Geriatr Cardiol 2020 Nov;17(11):680-693

Division of Cardiology, Daejeon St. Mary's hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.

Background: There are numerous but conflicting data regarding gender differences in outcomes following percutaneous coronary intervention (PCI). Furthermore, gender differences in clinical outcomes with acute myocardial infarction (AMI) following PCI in Asian population remain uncertain because of the under-representation of Asian in previous trials.

Methods: A total of 13, 104 AMI patients from Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH) between November 2011 and December 2015 were classified into male ( = 8021, 75.9%) and female ( = 2547, 24.1%). We compared the demographic, clinical and angiographic characteristics, 30-days and 1-year major adverse cardiac and cerebrovascular events (MACCE) in women with those in men after AMI by using propensity score (PS) matching.

Results: Compared with men, women were older, had more comorbidities and more often presented with non-ST segment elevation myocardial infarction (NSTEMI) and reduced left ventricular systolic function. Over the median follow-up of 363 days, gender differences in both 30-days and 1-year MACCE as well as thrombolysis in myocardial infarction minor bleeding risk were not observed in the PS matched population (30-days MACCE: 5.3% . 4.7%, log-rank = 0.494, HR = 1.126, 95% CI: 0.800-1.585; 1-year MACCE: 9.3% . 9.0%, log-rank = 0.803, HR = 1.032, 95% CI: 0.802-1.328; TIMI minor bleeding: 4.9% . 3.9%, log-rank = 0.215, HR = 1.255, 95% CI: 0.869-1.814).

Conclusions: Among Korean AMI population undergoing contemporary PCI, women, as compared with men, had different clinical and angiographic characteristics but showed similar 30-days and 1-year clinical outcomes. The risk of bleeding after PCI was comparable between men and women during one-year follow up.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2020.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729180PMC
November 2020
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