Publications by authors named "Yuichi Ozaki"

95 Publications

Cancer-related vulnerable lesions in patients with stable coronary artery disease.

Int J Cardiol 2021 Mar 26. Epub 2021 Mar 26.

Department of Cardiovascular Medicine, Wakayama Medical University, Wakayama, Japan.

Background: Coronary artery disease (CAD) has become a major cause of morbidity and mortality in cancer survivors. It is still unclear whether cancer history influences lesion characteristics. The purpose of this study was to investigate cancer-related lesion morphology in patients with CAD.

Methods: This study enrolled 400 patients with stable CAD. The patients were classified into a cancer survivor group (n = 69) and a noncancer group (n = 331). We investigated coronary lesion morphology by optical coherence tomography, and we assessed the prognosis in terms of both all-cause mortality and major adverse cardiovascular events (MACE).

Results: Adenocarcinoma was the most common histopathological diagnosis. Serum C-reactive protein levels were significantly higher in the cancer survivor group than in the noncancer group (cancer survivors 0.12 [0.05-0.42] mg/dL vs. noncancer 0.08 [0.04-0.17] mg/dL, p = 0.019). The cancer survivor group was more likely than the noncancer group to have thrombi (cancer survivors 30.4% vs. noncancer 15.4%, p = 0.004), and layered fibrotic plaques (LFPs; cancer survivors 18.8% vs. noncancer 3.6%, p < 0.0001). Cancer survivors had poorer outcomes than noncancer controls in terms of both all-cause mortality (p = 0.020) and MACE (p = 0.036).

Conclusions: Because of underlying inflammation, CAD patients with cancer had more high-risk lesions than those without cancer, which could result in poorer prognosis for the former. This result might inform the management of CAD in cancer patients in terms of secondary prevention.
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http://dx.doi.org/10.1016/j.ijcard.2021.03.050DOI Listing
March 2021

C-terminal peptide (hCTP) of human chorionic gonadotropin enhances in vivo biological activity of recombinant Japanese eel follicle-stimulating hormone and luteinizing hormone produced in FreeStyle 293-F cell lines.

Gen Comp Endocrinol 2021 Feb 2;306:113731. Epub 2021 Feb 2.

Tuna Aquaculture Division, Aquaculture Research Department, Fisheries Technology Institute, Japan Fisheries Research and Education Agency, 1551-8 Taira-machi, Nagasaki 851-2213, Japan. Electronic address:

Gonadotropins (Gths), follicle-stimulating hormone (Fsh), and luteinizing hormone (Lh) play central roles in the reproductive biology of vertebrates. In this study, recombinant single-chain Japanese eel Gths (rGth: rFsh and rLh), and recombinant chimeric Gths (rGth-hCTPs: rFsh-hCTP and rLh-hCTP; rGth-eCTPs: rFsh-eCTP and rLh-eCTP) with an extra O-glycosylation site (either a C-terminal peptide of human (hCTP) or equine (eCTP) chorionic gonadotropin), which are known to prolong the half-life of glycoprotein were produced in HEK293 cells and highly purified. Lectin blot analyses demonstrated that all these recombinant Gths contained N-glycans of the high mannose and complex types. In contrast, only rGth-hCTPs and rGth-eCTPs possessed highly sialylated O-linked oligosaccharides. Further analyses of glycans by liquid chromatography-mass spectrometry suggested that the species, amount, and degree of sialylation of N-glycans were comparable among recombinant Fshs and recombinant Lhs, while the amount of O-glycans with sialic acids in rGth-hCTPs was higher than that in the corresponding rGth-eCTPs. The serum levels of recombinant Gths in male eels significantly increased 12-24 h after a single injection of the Gths. The levels of rGth-hCTPs tended to be higher than those of the corresponding rGths and rGth-eCTPs throughout the experimental period, coinciding with the serum fluctuations of 11-ketotestosterone (11KT). The long-term treatment of male eels with these recombinant Gths also revealed the superiority of rGth-hCTPs in assisted reproduction; thus, the serum levels of 11KT and gonadosomatic indices in eels treated with rGth-hCTPs were higher than those in eels treated with the corresponding rGths and rGth-eCTPs. The induction of the entire process of spermatogenesis was only histologically observed in rGth-hCTPs-treated eels. These findings strongly suggest that hCTP enhances the in vivo biological activity of recombinant Japanese eel Gths due to the high abundance of O-linked glycans with sialylated antennae.
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http://dx.doi.org/10.1016/j.ygcen.2021.113731DOI Listing
February 2021

Japanese eel retinol dehydrogenases 11/12-like are 17-ketosteroid reductases involved in sex steroid synthesis.

Gen Comp Endocrinol 2021 May 1;305:113685. Epub 2020 Dec 1.

National Research Institute of Aquaculture, Japan Fisheries Research and Education Agency, 224-1 Hiruda, Tamaki, Watarai, Mie 519-0423, Japan. Electronic address:

The synthesis of 11-ketotestosterone (11KT) and estradiol-17β (E2), which play important roles in the regulation of gametogenesis in teleost fishes, is catalyzed by several steroidogenic enzymes. In particular, 17β-hydroxysteroid dehydrogenases (Hsd17bs) with 17-ketosteroid reducing activity (17KSR activity) are essential enzymes in the formation of these sex steroid hormones in the gonads and other tissues. Retinol dehydrogenase 11 (RDH11) has been suggested to be a novel tentative HSD17B (HSD17B15) in humans for a decade, however no definitive proof has been provided yet. In this study, three cDNAs related to human RDH11 were isolated from Japanese eel testis and characterized. Sequence similarity and phylogenetic analyses revealed their close relationship to human rdh11 and rdh12 gene products and they were designated as rdh11/12-like 1, rdh11/12-like 2, and rdh11/12-like 3. Three recombinant Rdh11/12-like proteins expressed in HEK293T cells catalyzed the transformation of estrone into E2 and androstenedione into testosterone. Only Rdh11/12-like 1 catalyzed the conversion of 11-ketoandrostenedione into 11KT. Tissue-distribution analysis by quantitative real-time polymerase chain reaction revealed, in immature male Japanese eel, that rdh11/12-like 1 and rdh11/12-like 2 are predominantly expressed in testis and brain, while rdh11/12-like 3 is expressed ubiquitously. Moreover, we analyzed the effects of gonadotropins and 11KT on the expression of the three rdh11/12-like mRNAs in the immature testis. In vitro incubation of immature testes with various doses of recombinant Japanese eel follicle stimulating hormone, luteinizing hormone, and 11KT indicated that the expression of rdh11/12-like 1 mRNA, rdh11/12-like 2, and rdh11/12-like 3 did not change. These findings suggest that the three Rdh11/12-like proteins metabolize sex steroids. Rdh11/12-like 1 may be one of the enzymes with 17KSR activity involved in the production of 11KT in the testis.
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http://dx.doi.org/10.1016/j.ygcen.2020.113685DOI Listing
May 2021

Prevalence, Features, and Prognosis of Artery-to-Artery Embolic ST-Segment-Elevation Myocardial Infarction: An Optical Coherence Tomography Study.

J Am Heart Assoc 2020 12 30;9(24):e017661. Epub 2020 Nov 30.

Department of Cardiovascular Medicine Wakayama Medical University Wakayama Japan.

Background The major underlying mechanisms contributing to acute coronary syndrome are plaque rupture, plaque erosion, and calcified nodule. Artery-to-artery embolic myocardial infarction (AAEMI) was defined as ST-segment-elevation myocardial infarction caused by migrating thrombus formed at the proximal ruptured plaque. The aim of this study was to investigate the prevalence and clinical features of AAEMI by using optical coherence tomography. Methods and Results This study retrospectively enrolled 297 patients with ST-segment-elevation myocardial infarction who underwent optical coherence tomography before percutaneous coronary intervention. Patients were divided into 4 groups consisting of plaque rupture, plaque erosion, calcified nodule, and AAEMI according to optical coherence tomography findings. The prevalence of AAEMI was 3.4%. The culprit vessel in 60% of patients with AAEMI was right coronary artery. Minimum lumen area at the culprit site was larger in AAEMI compared with plaque rupture, plaque erosion, and calcified nodule (4.0 mm [interquartile range (IQR), 2.2-4.9] versus 1.0 mm [IQR, 0.8-1.3] versus 1.0 mm [IQR, 0.8-1.2] versus 1.1 mm [IQR, 0.7-1.6], <0.001). Lumen area at the rupture site was larger in patients with AAEMI compared with patients with plaque rupture (4.4 mm [IQR, 2.5-6.7] versus 1.5 mm [IQR, 1.0-2.4], <0.001). In patients with AAEMI, the median minimum lumen area at the occlusion site was 1.2 mm (IQR, 1.0-2.1), 40% of them had nonstent strategy, and the 3-year major adverse cardiac event rate was 0%. Conclusions AAEMI is a rare cause for ST-segment-elevation myocardial infarction and has unique morphological features of plaque including larger lumen area at rupture site and smaller lumen area at the occlusion site.
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http://dx.doi.org/10.1161/JAHA.120.017661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955389PMC
December 2020

Supporting evidence for ST-segment elevation myocardial infarction from optical coherence tomography.

EuroIntervention 2020 Nov 17. Epub 2020 Nov 17.

Department of Cardiovascular Medicine, Shingu Municipal Medical Center, Shingu, Japan.

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http://dx.doi.org/10.4244/EIJ-D-20-00985DOI Listing
November 2020

Natural history of adapted Leaman score assessing coronary artery disease progression by computed tomography angiography: A 7 year follow-up report.

Cardiovasc Revasc Med 2020 Jul 26. Epub 2020 Jul 26.

Instituto do Coração (InCor), Universidade de São Paulo, São Paulo, São Paulo, Brazil; Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil. Electronic address:

Background: Coronary computed tomographic angiography (CCTA) provides a non-invasive assessment of the coronary artery tree. Computed Tomography - adapted Leaman Score (CT-LeSc) has been shown to be an independent predictor of cardiac events in coronary artery disease (CAD) patients with a score greater than 5 (high).

Purpose: To investigate the relationship between CT-LeSc and the progression of CAD and to provide vessel- and segment-level CAD qualification and quantification at baseline and 7-year follow-up.

Methods: Patients with multivessel CAD and CCTA assessments at baseline and follow-up were included. The CT-LeSc analysis was performed in a paired fashion. The patient-level scores and the differences between each phase were assessed by 2 analysts in an independent CoreLab.

Results: This study analyzed 248 coronary segments from 17 patients with a mean follow-up interval of 7.5 ± 0.6 years. The mean CT-LeSc at baseline and follow-up were 14.6 ± 4.2 and 16.9 ± 1.5, respectively, with an absolute increase of 2.3 ± 1.8. The mean cumulative increase of new lesions was 0.2 ± 0.2 per year. Over time, 14.6% of the non-obstructive lesions became obstructive, and 15.0% of the non-calcified plaques became calcified. There were 29 new lesions found at follow-up, and out of these, 16 were obstructive and 19 were non-calcified.

Conclusion: In patients at high-risk for cardiac events, as determined by CT-LeSc, there was an increase in CT-LeSc, obstructive lesions, and calcified plaques over the 7-year follow-up period. Most of the new lesions were obstructive and non-calcified. This is the first report showing long term serial imaging CCTA changes in a high-risk population.
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http://dx.doi.org/10.1016/j.carrev.2020.07.023DOI Listing
July 2020

Spatiotemporal expression of activin receptor-like kinase-5 and bone morphogenetic protein receptor type II in the ovary of shortfinned eel, Anguilla australis.

Comp Biochem Physiol B Biochem Mol Biol 2021 Jan 28;251:110509. Epub 2020 Sep 28.

Department of Zoology, University of Otago, PO Box 56, Dunedin 9054, New Zealand.

In the eel ovary, the expression of growth differentiation factor-9 (Gdf9) appears to be largely confined to the germ cell in early stages of oogenesis. However, both the target tissue and the function of Gdf9 in fish remain unknown. This study aimed to describe the abundance and localization of activin receptor-like kinase-5 (Alk5) and bone morphogenetic protein receptor type II (Bmpr2), which together mediate the Gdf9 signal, in the ovary of a basal teleost, the shortfinned eel, Anguilla australis, during early folliculogenesis. The cDNA encoding eel alk5 and bmpr2 genes were cloned, characterized and the transcript abundances of these receptors quantified by quantitative real-time PCR. Ovarian transcript abundance for both receptors, along with that of gdf9 and of its paralogue bmp15, increased from the previtellogenic to early vitellogenic stage. Localization of receptor mRNAs by in situ hybridization revealed that these receptors are located in the somatic cells surrounding the oocyte. Furthermore, tissue distribution analysis showed that the expression of alk5 and bmpr2 were highest in ovary and thyroid, respectively. Unexpectedly, however, bmpr2 mRNA levels were lower in the ovary than in any of the other 17 tissues examined, and indeed, lower than ovarian gdf9 transcript abundance. These findings, together with the ovarian expression pattern of Gdf9, suggest that Gdf9, and conceivably, Bmp15, from the oocyte can signal through receptors that are located on the somatic cells surrounding the oocyte; this, in turn, facilitates elucidation of the function of these growth factors during oogenesis in teleost fish.
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http://dx.doi.org/10.1016/j.cbpb.2020.110509DOI Listing
January 2021

Correlation between computed tomography adapted leaman score and computed tomography liver and spleen attenuation parameters for non-alcoholic fatty liver disease as well as respective inflammatory mediators.

Int J Cardiovasc Imaging 2020 Dec 22;36(12):2383-2391. Epub 2020 Sep 22.

Instituto Do Coração (InCor), Universidade de São Paulo, Sao Paulo, SP, Brazil.

Metabolic syndrome is a primary driver of vascular inflammation, plaque development, and atherosclerotic disease. The Computed Tomography-adapted Leaman Score (CT-LeSc) has been shown to be an independent predictor of cardiac events in coronary artery disease (CAD) patients but has never been studied for broader applicability. Non-alcoholic fatty liver disease (NAFLD) is associated with similar systemic inflammatory processes as CAD, and its presence as assessed by Computed Tomography Liver and Spleen Attenuation (CT-LSA) may impact on the extension of the CT-LeSc. The purpose of this study was to investigate the association between the CT-LeSc and NAFLD and to characterize and compare the inflammatory processes of each disease state. This was an exploratory study in which patients with known multivessel CAD who were scheduled to undergo percutaneous coronary intervention were included. CT-LeSc were graded on pre-existing criteria by two independent CoreLab analysts. CT-LSA parameters analyzed included the liver absolute attenuation value, liver and spleen attenuation difference and liver-to-spleen attenuation ratio and were scored by two independent CoreLab analysts as well. Inflammatory mediator analysis included routine laboratory draws for a variety of known signal molecules. The overall liver absolute attenuation value did not correlate significantly with the CT-LeSc, but the subgroup 50 to 65 HU showed moderately negative correlation (R =  - 0.629; p = 0.008). The overall liver and spleen attenuation difference did not correlate significantly with the CT-LeSc, but the subgroup 1 to 18 HU showed moderately positive correlation (R = 0.513; p = 0.017). The overall and subgroup liver-to-spleen attenuation ratio did not correlate with the CT-LeSc. The eosinophil and leukocyte ratio showed weakly negative correlation with the overall CT-LeSc (R =  - 0.4602; p = 0.008), and VCAM-1 showed moderately negative correlation with CT-LeSc < 16.0 (R =  - 0.5678; p = 0.022). Some CT-LSA parameters correlate with high risk CT-LeSc and may both provide complementary information for cardiovascular risk stratification. The significant metrics of liver absolute attenuation value and liver and spleen attenuation difference can be quickly completed in the clinical setting and may support a suspicion of CAD.
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http://dx.doi.org/10.1007/s10554-020-02026-wDOI Listing
December 2020

Near-Infrared Spectroscopy Intravascular Ultrasound Imaging: State of the Art.

Front Cardiovasc Med 2020 30;7:107. Epub 2020 Jun 30.

MedStar Cardiovascular Research Network, MedStar Washington Hospital Center, MedStar Health Research Institute, Washington, DC, United States.

Acute coronary syndromes (ACS) secondary to coronary vessel plaques represent a major cause of cardiovascular morbidity and mortality worldwide. Advancements in imaging technology over the last 3 decades have continuously enabled the study of coronary plaques via invasive imaging methods like intravascular ultrasound (IVUS) and optical coherence tomography (OCT). The introduction of near-infrared spectroscopy (NIRS) as a modality that could detect the lipid (cholesterol) content of atherosclerotic plaques in the early nineties, opened the potential of studying "vulnerable" or rupture-prone, lipid-rich coronary plaques in ACS patients. Most recently, the ability of NIRS-IVUS to identify patients at risk of future adverse events was shown in a prospective multicenter trial, the Lipid-Rich-plaque Study. Intracoronary NIRS-IVUS imaging offers a unique method of coronary lipid-plaque characterization and could become a valuable clinical diagnostic and treatment monitoring tool.
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http://dx.doi.org/10.3389/fcvm.2020.00107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338425PMC
June 2020

Increased plaque rupture forms peak incidence of acute myocardial infarction in winter.

Int J Cardiol 2020 Dec 14;320:18-22. Epub 2020 Jul 14.

Department of Cardiovascular Medicine, Wakayama Medical University, Wakayama, Japan. Electronic address:

Background: It has been widely documented that circannual variation has an impact on the incidence and prognosis of cardiovascular diseases. It is unclear why cold ambient temperature increase the incidence of acute myocardial infarction (AMI). We investigated the relationship between the ambient temperature at the onset of AMI, the morphology of the culprit lesion in patients with AMI.

Methods: We investigated 202 consecutive patients with AMI who underwent optical coherence tomography (OCT). The participants were divided into lower (n = 100) and higher (n = 102) temperature groups based on the ambient temperature. The culprit lesion morphology was compared between the two groups.

Results: The median temperature at the onset of AMI was 16.6 °C. The prevalence of plaque ruptures was higher at lower temperatures (lower 66% vs. higher 45%, p = .003), whereas OCT-erosion was more frequent in the higher temperature group (lower 13% vs. higher 26%, p = .021). The lower temperature group showed more cholesterol crystals (lower 71% vs. higher 54%, p = .014).

Conclusion: The peak incidence of AMI in the winter is formed by increased plaque rupture, suggesting environmental temperature has an influence on the pathogenesis of AMI.
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http://dx.doi.org/10.1016/j.ijcard.2020.07.011DOI Listing
December 2020

Insulin-like growth factors 1 and 2 regulate gene expression and enzymatic activity of in ovarian follicles of the yellowtail, .

Heliyon 2020 Jun 10;6(6):e04181. Epub 2020 Jun 10.

Seikai National Fisheries Research Institute, Japan Fisheries Research and Education Agency, Taira-machi, Nagasaki 851-2213, Japan.

There is accumulating evidence that insulin-like growth factors (IGFs), primary mediators of somatic growth, play an important role in fish reproduction. Previously, we showed that IGF-1 and IGF-2 are expressed in the ovarian follicle cells of the yellowtail () during the vitellogenic phase, suggesting that IGFs may be involved in ovarian steroidogenesis. In this study, we examined the effects of IGF-1 and IGF-2 on gene expression and activity of steroidogenic enzymes in yellowtail ovary . IGF-1 and IGF-2 had no effect on mRNA levels of several steroidogenesis-related genes (, , , , and ). However, both IGFs enhanced the transcription of in vitellogenic ovaries, although such up-regulation was not found in the ovary at the pre-vitellogenic stage. The stage-dependent effects of IGFs were correlated with changes in ovarian mRNA levels during the reproductive cycle: transcript abundances increased in conjunction with ovarian development. In addition, IGF-induced gene expression was significantly inhibited by wortmannin, suggesting that PI3 kinase plays an essential role in IGF-mediated ovarian steroidogenesis. Furthermore, IGF-1 and IGF-2 promoted the conversion of both progesterone and 17α-hydroxyprogesterone to androstenedione in vitellogenic ovaries, suggesting that both IGFs stimulated 17α-hydroxylase and C lyase activities. Taken together, these findings suggest that IGF-1 and IGF-2 act directly on follicle cells to stimulate steroid production through an increase in gene expression and enzymatic activity of via induction of PI3 kinase.
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http://dx.doi.org/10.1016/j.heliyon.2020.e04181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298419PMC
June 2020

Supporting evidence from optical coherence tomography for shortening dual antiplatelet therapy after drug-eluting stents implantation.

Expert Rev Cardiovasc Ther 2020 May 4;18(5):261-267. Epub 2020 May 4.

Section of Interventional Cardiology, MedStar Washington Hospital Center , Washington, DC, USA.

Introduction: Dual antiplatelet therapy (DAPT) is required for coronary artery disease treated with drug-eluting stents (DES) implantation. Shortening DAPT duration would be beneficial for patients with high bleeding risk.

Areas Covered: Early healing patterns, especially stent strut coverage, assessed by optical coherence tomography (OCT) as a surrogate of neointima have been investigated to make decisions on whether short DAPT would be a safe alternative. This review evaluates the OCT evidence (i.e. neointimal coverage of stent struts within 3 months) for shortening DAPT duration after DES implantation.

Expert Commentary: Shortening DAPT (i.e. within 3 months) duration after DES implantation might reduce complications including bleeding without increasing stent thrombosis. However, the optimal duration of DAPT after DES implantation is under discussion. Long-term assessment of short DAPT is required for the decision of the new guidelines regarding the recommended duration of DAPT.
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http://dx.doi.org/10.1080/14779072.2020.1759421DOI Listing
May 2020

Novel Indices of Coronary Physiology: Do We Need Alternatives to Fractional Flow Reserve?

Circ Cardiovasc Interv 2020 04 16;13(4):e008487. Epub 2020 Apr 16.

MedStar Washington Hospital Centre, Interventional Cardiology Department, Washington, DC (Y.O., H.M.G.-G., A.H.-K., E.S., K.D., R.W.).

Fractional flow reserve is the current invasive gold standard for assessing the ischemic potential of an angiographically intermediate coronary stenosis. Procedural cost and time, the need for coronary vessel instrumentation, and the need to administer adenosine to achieve maximal hyperemia remain integral components of invasive fractional flow reserve. The number of new alternatives to fractional flow reserve has proliferated over the last ten years using techniques ranging from alternative pressure wire metrics to anatomic simulation via angiography or intravascular imaging. This review article provides a critical description of the currently available or under-development alternatives to fractional flow reserve with a special focus on the available evidence, pros, and cons for each with a view towards their clinical application in the near future for the functional assessment of coronary artery disease.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.119.008487DOI Listing
April 2020

Coronary Artery Disease Assessed by Computed Tomography-Based Leaman Score in Patients With Low-Risk Transcatheter Aortic Valve Implantation.

Am J Cardiol 2020 04 28;125(8):1216-1221. Epub 2020 Jan 28.

Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, District of Columbia.

We aimed to evaluate the burden of coronary artery disease (CAD) using the computed tomography (CT) Leaman score in low-risk transcatheter aortic valve implantation (TAVI) patients. The extent of CAD in low-risk patients with aortic stenosis who are candidates for TAVI has not been accurately quantified. The CT Leaman score was developed to quantify coronary CT angiography (CCTA) atherosclerotic burden and has been validated to evaluate the extent of CAD. CT Leaman score >5 has been associated with an increase in major adverse cardiac events over long-term follow-up. The study population included patients enrolled in the Low Risk TAVI trial who underwent CCTA before the procedure. For the CT Leaman score, we used 3 sets of weighting factors: (1) location of coronary plaques, (2) type of plaque, and (3) degree of stenosis. A total of 200 patients were enrolled in the Low Risk TAVI trial. Excluded were 31 patients who had no analyzable CCTA imaging. For the remaining 169 patients, the mean CT Leaman score was 6.27 ± 0.27, of whom 102 (60.4%) had CT Leaman score >5. Nearly all analyzed patients (97%) had coronary plaques. Furthermore, 33 patients (19.5%) had potentially obstructive coronary plaques (>50% stenosis by CCTA) in proximal segments. Most low-risk TAVI patients have significant CAD burden by CCTA. It should be a priority for future TAVI devices to guarantee unimpeded access to the coronary arteries for selective angiography and interventions.
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http://dx.doi.org/10.1016/j.amjcard.2020.01.022DOI Listing
April 2020

17β-Hydroxysteroid dehydrogenase type 12a responsible for testicular 11-ketotestosterone synthesis in the Japanese eel, Anguilla japonica.

J Steroid Biochem Mol Biol 2020 04 25;198:105550. Epub 2019 Nov 25.

National Research Institute of Aquaculture, Japan Fisheries Research and Education Agency, Tsuiura, Kamiura, Saiki, Oita 879-2602, Japan. Electronic address:

The production of 11-ketotestosterone (11KT), an important steroid hormone in piscine spermatogenesis, is regulated by the pituitary gonadotropins [Gths: follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh)] and it is synthesized by catalytic reactions involving several steroidogenic enzymes. Among these enzymes, the role of 17β-hydroxysteroid dehydrogenases (Hsd17bs) that exhibited 17-ketosteroid reducing activity (17KSR activity) responsible for 11KT synthesis is still poorly understood. In the present study, for the deeper understanding of testicular 11KT biosynthesis, we first investigated the steroidogenic pathway to produce 11KT in Japanese eel testis. In vitro incubation of the testis with androstenedione (A4) and the subsequent analysis of the metabolites by thin-layer chromatography indicated that 11KT was synthesized from A4 via 11β-hydroxyandrostenedione (11OHA4) and 11-ketoandrostenedione (11KA4), which indicated that the steroidogenic enzyme exhibiting the 17KSR activity responsible for converting 11KA4 to 11KT is crucial for 11KT production. Subsequently, cDNAs encoding three candidate enzymes, Hsd17b type3 (Hsd17b3), Hsd17b type12a (Hsd17b12a), and 20β-hydroxysteroid dehydrogenase type2 (Hsd20b2), potentially with the 17KSR activity were isolated and characterized in the Japanese eel. The isolated hsd17b3, hsd17b12a, and hsd20b2 cDNAs putatively encoded 308, 314, and 327 amino acid residues with high homology to those of other vertebrate counterparts, respectively. The Hsd17b3, Hsd17b12a, and Hsd20b2 expressed either in HEK293T or in Hepa-E1 converted 11KA4 to 11KT. Tissue-distribution analysis by quantitative real time PCR revealed that hsd17b12a and hsd20b2 mRNAs were detected in the testis, while hsd17b3 mRNA was not detectable. Furthermore, we examined the effects of Gths on the 17KSR activity and the expression of the candidate genes in the immature testis. The 17KSR activity was upregulated by administration of Gths. Furthermore, only expression of hsd17b12a among three candidates was upregulated by Gths as well as the 17KSR activity. These findings strongly suggested that Hsd17b12a is one of the enzymes with 17KSR activity responsible for 11KT synthesis in the testis of Japanese eel.
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http://dx.doi.org/10.1016/j.jsbmb.2019.105550DOI Listing
April 2020

Comparison of clinical outcomes between Magmaris and Orsiro drug eluting stent at 12 months: Pooled patient level analysis from BIOSOLVE II-III and BIOFLOW II trials.

Int J Cardiol 2020 02 6;300:60-65. Epub 2019 Nov 6.

Lukaskrankenhaus Neuss, Neuss, Germany.

Background: The aim of this study was to compare the 12-month clinical outcomes of patients treated with Magmaris or Orsiro. Second generation drug-eluting absorbable metal scaffold Magmaris (Dreams 2G) has proved to be safe and effective in the BIOSOLVE-II study. Similarly, biodegradable polymer sirolimus-eluting stent, Orsiro has shown notable clinical results even in all-comer populations.

Methods: Magmaris group patients were taken from the BIOSOLVE-II and BIOSOLVE-III trials, while the patients from Orsiro group were enrolled in BIOFLOW-II trial. The primary outcome was explored using a time-to-event assessment of the unadjusted clinical outcomes for target lesion failure (TLF) at 12 months, followed by a multivariate analysis adjusting for all the significantly different covariates between the groups.

Results: The study population consisted of 482 patients (521 lesions), 184 patients (189 lesions) in Magmaris group and 298 patients (332 lesions) in Orsiro group. The mean age was 65.5 ± 10.8 and 62.7 ± 10.4 years in Magmaris and Orsiro groups, respectively (p = 0.005). Magmaris and Orsiro unadjusted TLF rates were 6.0 and 6.4% with no significant difference between the groups (p = 0.869). In the multivariate analysis, there were no meaningful differences between Magmaris and Orsiro groups. Finally, none of the groups presented device thrombosis cases at 12 months.

Conclusion: At 12 months there were no significant differences between Magmaris and Orsiro groups neither in the unadjusted assessment nor in the multivariate analysis for target lesion failure. These results should be taken as hypothesis generating and may warrant a head to head comparison on a randomized fashion.
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http://dx.doi.org/10.1016/j.ijcard.2019.11.003DOI Listing
February 2020

Second-Generation Drug-Eluting Resorbable Magnesium Scaffold: Review of the Clinical Evidence.

Cardiovasc Revasc Med 2020 01 22;21(1):127-136. Epub 2019 Oct 22.

Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC, USA.

Since October 8, 2013, the second-generation drug-eluting resorbable magnesium scaffold (RMS) has been used to treat coronary lesions. At present, the second-generation drug-eluting RMS is clinically available in Europe, some South American countries, and some Asian and African countries. Furthermore, patients are currently being enrolled in ongoing post-marketing trials. This device has the potential to be an alternative to drug-eluting stents in the future, but there is not yet sufficient evidence. This review provides the latest available evidence, comparison with other bioresorbable scaffolds, future perspectives, and discussion of clinical case reports with second-generation drug-eluting RMS. SUMMARY: Favorable outcomes have been reported after second-generation drug-eluting RMS implantation. More long-term clinical outcomes for this novel device are still required in the future.
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http://dx.doi.org/10.1016/j.carrev.2019.10.012DOI Listing
January 2020

Feasibility and Clinical Significance of In Vivo Cholesterol Crystal Detection Using Optical Coherence Tomography.

Arterioscler Thromb Vasc Biol 2020 01 17;40(1):220-229. Epub 2019 Oct 17.

From the Department of Cardiovascular Medicine (Y.K., A. Tanaka, A. Taruya, M.K., T.N., Y.O., Y.M., H.K., T. Kubo, T.A.), Wakayama Medical University, Japan.

Objective: Cholesterol crystals (CCs) are frequently found at the site of acute myocardial infarctions (AMIs), but the role of CCs in the onset of AMI remains unclear due to the lack of validated in vivo imaging tools. The aim of this study was to validate the ability of optical coherence tomography (OCT) to detect CCs and to compare the prevalence and distribution of CCs in patients with AMIs and stable angina pectoris. Approach and Results: CC assessment using OCT were compared with histopathology results in 45 coronary samples. We investigated 152 consecutive patients with AMIs and 41 patients with single vessel-diseased stable angina pectoris. Based on the presence of plaque ruptures (PR), AMI patients were divided into 2 groups: those with PR (n=112) and those without PR (n=40). CCs invading fibrous caps were defined as superficial-type CCs. A multivariable logistic regression analysis was performed to determine PR predictors. The sensitivity and specificity of OCT for detecting CCs were 68% and 92%, respectively. The prevalence of plaques with CCs was higher in the AMI with PR group (AMI with PR 81%, AMI without PR 48%, stable angina pectoris 39%, <0.01). A multivariable logistic model showed that superficial-type CCs and thin-cap fibroatheromas were positive predictors for PR.

Conclusions: OCT has a high specificity and modest sensitivity for the detection of CCs. The combination of CCs invading fibrous cap and thin-cap fibroatheromas detected by OCT may better identify rupture-prone plaques.
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http://dx.doi.org/10.1161/ATVBAHA.119.312934DOI Listing
January 2020

Comparison of quantitative flow ratio value of left anterior descending and circumflex coronary artery in patients with Takotsubo syndrome.

Int J Cardiovasc Imaging 2020 Jan 1;36(1):3-8. Epub 2019 Oct 1.

Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC, USA.

Takotsubo syndrome (TTS) is an acute cardiac event without epicardial coronary obstruction but often with reversible ventricular motion abnormalities. Quantitative flow ratio (QFR) is a novel approach to evaluate the coronary stenosis significance on the basis of 3-dimensional quantitative coronary angiography (3D-QCA) and contrast flow by Thrombolysis in Myocardial Infarction frame count. This study aimed to evaluate and compare the QFR value in the left anterior descending artery (LAD) and the left circumflex artery (LCx) in patients with TTS. This retrospective and observational study enrolled 30 patients with TTS who underwent coronary angiography. We evaluated the QFR data using the 3D-QCA analysis and compared the QFR data in the LAD and the LCx. No significant differences were observed in terms of flow velocity, percent diameter stenosis, minimum lumen diameter, and reference diameter between LAD and LCx. However, vessel QFR in the LAD was significantly reduced compared with that in the LCx (0.98 [0.94 to 0.99] vs. 1.00 [0.99 to 1.00], P < 0.001). Ejection fraction at baseline and initial troponin-I levels were not correlated with the vessel QFR both in the LAD and the LCx. The QFR value in the LAD was significantly reduced compared to that in the LCx in patients with TTS.
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http://dx.doi.org/10.1007/s10554-019-01703-9DOI Listing
January 2020

Targeted mutagenesis of the ryanodine receptor by Platinum TALENs causes slow swimming behaviour in Pacific bluefin tuna (Thunnus orientalis).

Sci Rep 2019 09 25;9(1):13871. Epub 2019 Sep 25.

Seikai National Fisheries Research Institute, Japan Fisheries Research and Education Agency, Nagasaki, 851-2213, Japan.

In bluefin tuna aquaculture, high mortalities of hatchery-reared juveniles occur in sea cages owing to wall collisions that are caused by high-speed swimming in panic due to changes in illuminance. Here, we report that targeted gene mutagenesis of the ryanodine receptor (RyR1b), which allows the sarcoplasmic reticulum to release Ca in fast skeletal muscle, using highly active Platinum TALENs caused slow swimming behaviour in response to external stimuli in Pacific bluefin tuna (PBT) larvae. This characteristic would be a useful trait to prevent wall collisions in aquaculture production. A pair of Platinum TALENs targeting exons 2 and 43 of the PBT ryr1b gene induced deletions in each TALEN target site of the injected embryos with extremely high efficiency. In addition, ryr1b expression was significantly decreased in the mutated G0 larvae at 7 days after hatching (DAH). A touch-evoked escape behaviour assay revealed that the ryr1b-mutated PBT larvae swam away much less efficiently in response to mechanosensory stimulation at 7 DAH than did the wild-type larvae. Our results demonstrate that genome editing technologies are effective tools for determining the functional characterization of genes in a comparatively short period, and create avenues for facilitating genetic studies and breeding of bluefin tuna species.
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http://dx.doi.org/10.1038/s41598-019-50418-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761128PMC
September 2019

Prognostic Value of Human Peripheral Monocyte Subsets for Future Coronary Events in Patients Without Significant Coronary Artery Stenosis.

Circ J 2019 10 11;83(11):2250-2256. Epub 2019 Sep 11.

Department of Cardiovascular Medicine, Wakayama Medical University.

Background: Monocytes in human peripheral blood are heterogeneous and can be divided into 2 groups, inflammatory and pro-inflammatory, according to the differential expression of CD14 and CD16. Pro-inflammatory monocytes (CD14CD16) seem to contribute to the development of coronary artery disease. This study aimed to investigate the involvement of specific human peripheral monocyte subsets in the development of future coronary events.Methods and Results:We enrolled 271 patients who were suspected to have either stable angina pectoris or silent myocardial ischemia and underwent coronary angiography (CAG). Two monocyte subsets (CD14CD16and CD14CD16) were measured by flow cytometry. Patients who did not undergo coronary artery revascularization at initial CAG were followed as the medical therapy group, which included 136 patients among whom 15 had future coronary events. The frequency of CD14CD16monocytes was significantly higher in patients who had future coronary events than in those who did not (P<0.01). Furthermore, the frequencies of CD14CD16monocyte were not significantly different between patients who had future coronary events and those who underwent coronary revascularization at initial CAG (P<0.33). Multivariate analysis revealed that the frequency of CD14CD16monocytes was an independent predictor for future coronary events (P<0.01).

Conclusions: An increase in the abundance of human peripheral pro-inflammatory monocytes is related to the development of future coronary events.
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http://dx.doi.org/10.1253/circj.CJ-19-0520DOI Listing
October 2019

Functional analysis of recombinant single-chain Japanese eel Fsh and Lh produced in FreeStyle 293-F cell lines: Binding specificities to their receptors and differential efficacy on testicular steroidogenesis.

Gen Comp Endocrinol 2020 01 7;285:113241. Epub 2019 Aug 7.

National Research Institute of Aquaculture, Japan Fisheries Research and Education Agency, 224-1 Hiruda, Tamaki, Watarai, Mie 519-0423, Japan. Electronic address:

Pituitary gonadotropins, follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh), play central roles in the control of gonadal development of vertebrates. In mammals, Fsh and Lh exclusively activate their respective cognate receptors: Fsh receptor (Fshr) in the Sertoli cell and Lh/choriogonadotropin receptor (Lhcgr) in the Leydig cell. In teleosts, the distinct functions of Fsh and Lh and information on cellular localization of their receptors are still poorly understood. Recently we established FreeStyle 293-F cell lines producing recombinant Japanese eel Fsh and Lh (reFsh and reLh), which form a single chain consisting of a common α-subunit and β-subunits. In this study, we conducted functional analyses of reFsh and reLh, focusing on the binding specificities to their receptors and effects on testicular steroidogenesis in vitro. Assays with gonadotropin receptors-expressing COS-7 cells indicated reFsh stimulated its cognate receptor, meanwhile reLh activated both receptors. Although results of in vitro incubations showed that reFsh and reLh induced testicular 11-ketotestosterone production in a dose and time-dependent manner by upregulating expression of steroidogenic enzymes, the effective doses of reLh were apparently lower and the effects of reLh emerged faster in comparison with reFsh. Results of quantitative real-time PCR using testicular cell fractions showed that fshr and lhcgr1 mRNA were detected both in Sertoli and Leydig cells. These analyses revealed that reFsh and reLh were biologically active and hence will be useful for future studies. Moreover, our data showed that both eel Fsh and Lh acted as steroidogenic hormones through their receptors in testicular somatic cells; however, Lh was more potent on androgen production, implying differential functions on spermatogenesis.
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http://dx.doi.org/10.1016/j.ygcen.2019.113241DOI Listing
January 2020

Impact of two formulas to calculate percentage diameter stenosis of coronary lesions: from stenosis models (phantom lesion model) to actual clinical lesions.

Int J Cardiovasc Imaging 2019 Dec 27;35(12):2139-2146. Epub 2019 Jul 27.

Division of Interventional Cardiology - MedStar Cardiovascular Research Network, MedStar Washington Hospital Center, Georgetown University, Washington, USA.

Percentage diameter stenosis (%DS) by angiography is still commonly used to determine luminal obstruction of coronary artery disease (CAD) lesions. While visual estimation of %DS is widespread, because of high inter-operator variability, quantitative coronary arteriography (QCA) analysis is the gold standard. There are two %DS formulas: %DS1 averages the proximal and distal reference vessel diameter (RVD); %DS2 interpolates the RVD. This study aims to evaluate the difference between %DS assessed by QCA in two datasets, phantom lesion models and CAD patients. Ten phantom lesion models (PLMs) and 354 CAD lesions from the FIRST trial were assessed by QCA. In the latter, two scenarios were assessed: Scenario A (worst view), the most common approach in the clinical setting; and Scenario B (average of two complementary views), the standard core-laboratory analysis. In the PLMs, %DS1 and %DS2 mean ± standard deviation (median) was 58.5 ± 21.7 (61.6) and 58.7 ± 21.6 (61.8), respectively, with a signed difference of - 0.2% ± 0.3% (- 0.1%). In Scenario A, the mean %DS1 was 43.8 ± 9.1 (43.3) and 44.0 ± 9.1 (42 .9) in %DS2. In Scenario B, the mean %DS1 was 45.3 ± 8.8 (45.1) and 45.5 ± 9.0 (45.1) in %DS2. The signed difference was - 0.2% ± 2.4% (0.0%) and - 0.2% ± 2.1% (0.0%) in Scenario A and B, respectively. These differences between formulas ranged from - 1.2 to 0.5% for the phantom cases compared to - 17.7% to 7.7% in Scenario A and to - 15.5% to 7.1% in Scenario B. Although the overall means of the formulas provide similar results, significant lesion-level differences are observed. The use of the worst view versus the average of two views provided similar results.
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http://dx.doi.org/10.1007/s10554-019-01672-zDOI Listing
December 2019

The Impact of Blood Pressure Variability on Coronary Arterial Lumen Dimensions as Assessed by Optical Coherence Tomography in Patients with ST-Elevation Myocardial Infarction.

Cardiovasc Revasc Med 2019 Sep 4;20(9):768-774. Epub 2019 Jun 4.

Oxford Heart Centre, NIHR Biomedical Research Centre, Oxford University Hospitals, Oxford, UK. Electronic address:

Background: Patients with ST-elevation Myocardial Infarction treated by primary percutaneous coronary intervention (PPCI) experience drastic hemodynamic systemic changes (i.e., blood pressure) during the different phases of the procedure. Optical coherence tomography is often used to unveil the underlying cause of STEMI (pre-PCI) and to optimize stent implantation (post-PCI). The impact of blood pressure variability on coronary lumen remains uncertain. This study aimed to investigate the relationship between blood pressure variability, before and after PCI, and coronary arterial lumen dimensions of the infarct-related artery.

Methods: We measured systolic, diastolic and mean arterial blood pressure (SBP, DBP, and MAP; respectively) at pre- and post-PCI. Frequency-domain optical coherence tomography (FD-OCT) imaging was performed at the same time points. Offline quantitative image analyses were performed to assess the average and minimum lumen area (LA). Δ blood pressure (after and before the PCI) was then calculated.

Results: A total of 14 ST-segment elevation myocardial infarction (STEMI) patients were included. 84.2% of enrolled patients were male with a mean age of (58 ± 10.7 years). Roughly two-thirds (57.8%) had hypertension. The mean SBP was (112.6 mm Hg ± 16.1) and (117.2 mm Hg ± 20.9), pre- and post-stenting, respectively; the range of the observed SBP differences (between pre- and post-PCI) went from -25 to +23 mm Hg. Pre- and post-stenting mean average LA were (7.1 ± 2.5 mm and 6.8 ± 2.3 mm; respectively). There were poor correlations between ΔSBP and Δ mean minimum LA. A similar pattern was observed with ΔDBP and ΔMAP.

Conclusion: Despite significant hemodynamic variability, the difference in lumen cross-sectional area, between pre- and post-coronary artery stenting was minimal. This study supports the use of OCT lumen areas to inform clinical decisions during PPCI.
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http://dx.doi.org/10.1016/j.carrev.2019.05.027DOI Listing
September 2019

Effect of Statin Therapy on Fibrous Cap Thickness in Coronary Plaque on Optical Coherence Tomography - Review and Meta-Analysis.

Circ J 2019 06 22;83(7):1480-1488. Epub 2019 May 22.

Section of Interventional Cardiology, MedStar Washington Hospital Center.

Background: Statin therapy has been shown to result in coronary plaque regression, but the relationship between statin use and stabilization of coronary plaque has not been elucidated. We conducted a systematic review and meta-analysis to evaluate the effect of statin therapy on fibrous cap thickness (FCT) on optical coherence tomography (OCT).Methods and Results:Nine OCT studies (6 randomized controlled trials and 3 observational studies) were enrolled with a total of 341 patients (390 lesions). Arms of the studies were grouped according to statin type and/or dose. Random effects meta-analysis was used to estimate a pooled mean change in FCT from baseline to follow-up. The overall effect mean FCT change was 67.7 µm (95% CI: 51.4-84.1, I=95.0%, P<0.001). All statin groups had an increase in FCT, but the magnitude of the increase differed according to the statin. Two homogeneous subgroups with I=0 were identified: mean FCT change was 27.8 µm (for subgroup atorvastatin 5 mg and rosuvastatin), and 61.9 µm (for subgroup atorvastatin 20 mg, fluvastatin 30 mg, and pitavastatin 4 mg). On meta-regression modeling, statin therapy alone explained most of the change in FCT.

Conclusions: Statin therapy induced a significant increase in FCT as assessed on OCT, independent of coronary risk factors and other medications.
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http://dx.doi.org/10.1253/circj.CJ-18-1376DOI Listing
June 2019

First Report of Edge Vascular Response at 12 Months of Magmaris, A Second-Generation Drug-Eluting Resorbable Magnesium Scaffold, Assessed by Grayscale Intravascular Ultrasound, Virtual Histology, and Optical Coherence Tomography. A Biosolve-II Trial Sub-Study.

Cardiovasc Revasc Med 2019 05 18;20(5):392-398. Epub 2019 Feb 18.

Interventional Cardiology Department, MedStar Washington Hospital Center, Washington, DC, USA.

Introduction And Objective: The edge vascular response (EVR) remains unknown in second generation drug-eluting Resorbable Magnesium Scaffold (RMS), such as Magmaris. The aim of the study was to evaluate tissue modifications in the RMS edges over time, assessed by different invasive imaging modalities.

Methods: The patients treated with the device were assessed by optical coherence tomography (OCT), grayscale intravascular ultrasound (IVUS), and virtual histology IVUS at baseline and 12 months. The EVR study performed a segment- and frame-level analysis of the 5 mm segments proximal and distal of the actual RMS.

Results: The segment-level grayscale IVUS (n = 10), virtual histology IVUS (n = 10), and OCT (n = 18) analysis did not show any significant changes after 12 months, except for a fibrous plaque area (FPA) reduction of 0.5mm (p = 0.017) in the proximal segment compared to baseline. In the frame-level analysis, IVUS evaluation revealed a vessel area decreased 2.80 ± 1.43 mm (p = 0.012) and 2.49 ± 1.53 mm (p = 0.022) in 2 proximal frames. This was accompanied by plaque area reduction of 0.88 ± 0.70 mm (p = 0.048) and a FPA decreased by 0.63 ± 0.48 mm (p = 0.004) in one proximal frame. In 1 distal frame, there was a dense calcium area reduction of 0.10 ± 0.12 mm (p = 0.045), FPA and fibrous fatty plaque increased 0.54 ± 0.53 mm (p = 0.023) and 0.17 ± 0.16 mm (p = 0.016), respectively. By OCT, there was a lumen area decrease of 0.76 ± 1.51 mm (p = 0.045) in a distal frame.

Conclusion: At 12 months, Magmaris EVR assessment does not show overall significant changes, except for a fibrous plaque area reduction in the proximal segment. This could be translated as a benign healing process at the edges of the RMS.

Summary: The edge vascular response (EVR) remains unknown in second generation drug-eluting absorbable metal scaffolds (RMS), such as Magmaris. Patients treated with the device were assessed by multi invasive imaging modalities [i.e. optical coherence tomography (OCT), grayscale intravascular ultrasound (IVUS), and virtual histology IVUS] evaluating the tissue changes over time in the segment- and frame-level analysis of the 5 mm segments proximal and distal of the actual RMS. As a result, after 12 months, Magmaris EVR assessment does not show overall significant changes, except for a fibrous plaque area reduction in the proximal segment, translating a benign healing process at the edges of the RMS.
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http://dx.doi.org/10.1016/j.carrev.2019.02.019DOI Listing
May 2019

Lesion characteristics and prognosis of acute coronary syndrome without angiographically significant coronary artery stenosis.

Eur Heart J Cardiovasc Imaging 2020 02;21(2):202-209

Department of Cardiovascular Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama 641-8509, Japan.

Aims: While patients with acute coronary syndrome (ACS) presenting with non-obstructive coronary artery disease (CAD) are at high risk for cardiovascular mortality and morbidity, detailed lesion characteristics are unclear. The aim of this study was to investigate the lesion characteristics and prognosis of ACS with non-obstructive CAD.

Methods And Results: This study consisted of 82 consecutive ACS patients without obstructive CAD who underwent optical coherence tomography (OCT). Based on the presence of high-risk lesions (HL) in the culprit artery, we classified the patients into two groups: HL group and non-high-risk lesions (NHL) group. A systematic clinical follow-up was performed at our outpatient clinic for up to 24 months. Our endpoint was recurrence of ACS with obstructive CAD. OCT revealed that 42 (51.2%) of 82 patients had hidden HL in the culprit artery, including ruptured plaque (15.9%), calcified nodule (11.0%), spontaneous coronary artery dissection (8.5%), lone thrombus (8.5%), thin-cap fibroatheroma (6.1%), and plaque erosion (1.2%). During angiography, 5 (11.9%) HL patients complained of chest pain without ST elevation. Patients in the HL group had poorer prognoses than those in the other groups (P = 0.040).

Conclusion: Hidden high-risk lesions accompany ACS patients without obstructive CAD, resulting in poorer outcomes. Vascular injury itself might provoke acute chest pain.
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http://dx.doi.org/10.1093/ehjci/jez079DOI Listing
February 2020

Expressional regulation of gonadotropin receptor genes and androgen receptor genes in the eel testis.

Gen Comp Endocrinol 2019 09 19;280:123-133. Epub 2019 Apr 19.

Department of Zoology, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand.

Receptors for follicle-stimulating hormone (Fshr), luteinizing hormone (Lhcgr1 and Lhcgr2) and androgens (Ara and Arb) transduce the hormonal signals that coordinate spermatogenesis, but the factors that regulate the abundance of these transducers in fish testes remain little-understood. To mend this paucity of information, we first determined changes in transcript abundance for these receptors (fshr, lhcgr1, ara and arb) during spermatogenesis induced by human chorionic gonadotropin (hCG) injection in the eel, Anguilla australis. We related our findings to testicular production of the fish androgen, 11-ketotestosterone (11-KT), and to the levels of the transcripts encoding steroidogenic acute regulatory protein (star) and 11β-hydroxylase (cyp11b), and subsequently evaluated the effects of hCG or 11-KT on mRNA levels of these target genes in vitro. Testicular 11-KT production was greatly increased by hCG treatment, both in vivo and in vitro, and associated with up-regulation of star and cyp11b transcripts. In situ hybridization indicated that testicular fshr mRNA levels were higher in the early stages of hCG-induced spermatogenesis, while lhcgr1 transcripts were most abundant later, once spermatids were observed. In vitro experiments further showed that hCG and its steroidal mediator 11-KT significantly increased fshr transcript abundance. These data provide new angles on the interactions between gonadotropin and androgen signaling during early spermatogenesis. Increases in levels of 11-KT following hCG injection elevated testicular fshr mRNA levels augmenting Fsh sensitivity in the testis. This evidence is suggestive of a positive feedback loop between gonadotropins and 11-KT that may be key to regulating early spermatogenesis in fish.
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http://dx.doi.org/10.1016/j.ygcen.2019.04.020DOI Listing
September 2019

Effects of Cangrelor as Adjunct Therapy to Percutaneous Coronary Intervention.

Am J Cardiol 2019 04 25;123(8):1228-1238. Epub 2019 Jan 25.

Division of Interventional Cardiology, MedStar Washington Hospital Center, Washington, District of Columbia. Electronic address:

Percutaneous coronary intervention (PCI) in patients with angiographic evidence of intracoronary thrombus is associated with in-hospital and 30-day adverse clinical outcomes. Cangrelor, a direct, rapid-onset acting intravenous P2Y receptor inhibitor, has been proved to be effective by reducing peri-PCI ischemic complications in subjects who underwent PCI. This study aimed to assess the angiographic and in-hospital clinical outcomes in all-comer patients receiving cangrelor immediately before PCI at a tertiary care center. The study analyzed consecutive unselected subjects treated with cangrelor at the time the decision was made to proceed with PCI. At the end of the procedure, all patients were transitioned to oral antiplatelet therapy. The target lesion angiographic assessment of Thrombolysis in myocardial infarction flow grade (TIMI-Flow), TIMI-thrombus grade (TIMI-Thrombus), myocardial blush grade, and TIMI-myocardial perfusion grade (TMPG) was performed before and post-PCI. Clinical events were recorded during the procedure and at discharge. In total, 223 patients (244 lesions) were included in the analysis (106, 97, and 20 patientswith TIMI-Flow 0/1, TIMI-Flow 2/3, and cardiogenic shock, respectively). The overall mean age was 63 ± 12 years, 70% men and 38% with diabetes mellitus. Acute myocardial infarction was the main presentation (72%). The use of cangrelor improved TIMI-Flow, MGB, TMPG, and TIMI-Thrombus in patients with initial TIMI-Flow 0 to 2. Major bleeding rate was 2.0%. In conclusion, cangrelor was effective and safe in restoring TIMI-Flow 3, reducing thrombus burden and improving myocardial blush grade and TMPG when administered to unselected subjects who underwent PCI. Therefore, cangrelor should be considered in patients presenting with intracoronary thrombus before intervention.
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http://dx.doi.org/10.1016/j.amjcard.2019.01.031DOI Listing
April 2019