Publications by authors named "Zhisheng Jiang"

65 Publications

Safety analysis of early oral feeding after esophagectomy in patients complicated with diabetes.

J Cardiothorac Surg 2021 Mar 26;16(1):56. Epub 2021 Mar 26.

Bengbu Medical College, Bengbu, China.

Objective: To evaluate the safety of early oral feeding in patients with type II diabetes after radical resection of esophageal carcinoma.

Methods: The clinical data of 121 patients with type II diabetes who underwent radical resection of esophageal carcinoma in the department of cardiothoracic surgery of Jinling Hospital from January 2016 to December 2018 were retrospectively analyzed. According to the median time (7 days) of the first oral feeding after surgery, the patients were divided into early oral feeding group (EOF, feeding within 7 days after surgery, 67 cases) and late oral feeding group (LOF, feeding after 7 days, 54 cases). Postoperative blood glucose level, incidence of complications, nutritional and immune indexes, inflammatory indexes, normalized T12-SMA (the postoperative/preoperative ratio of vertical spinal muscle cross-sectional area at the 12th thoracic vertebra level) and QLQ-C30 (Quality Of Life Questionnaire) scores were recorded and compared in the two groups.

Results: There was no statistical difference in preoperative nutritional index and postoperative complication rates between the EOF and LOF group (p > 0.05). The postoperative nutritional index (ALB, PA, TRF, Hb) and immune index (IgA, IgG, IgM) of the EOF group were higher than those of the LOF group (p < 0.05), and the inflammatory indicators (CRP, IL-6) of the EOF group were significantly lower than those of the LOF group (p < 0.05). Moreover, postoperative T12-SMA variation and QLQ-C30 scores of the EOF group were higher than those in LOF group (p < 0.05).

Conclusions: Early oral feeding is safe and feasible for patients with type II diabetes after radical resection of esophageal cancer, and it can improve short-term nutritional status and postoperative life quality of the patients.
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http://dx.doi.org/10.1186/s13019-021-01410-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995741PMC
March 2021

FAM83A and FAM83A-AS1 both play oncogenic roles in lung adenocarcinoma.

Oncol Lett 2021 Apr 17;21(4):297. Epub 2021 Feb 17.

Department of Cardiothoracic Surgery, Jinling Hospital, School of Medicine, Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.

Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Nevertheless, the detailed molecular mechanisms of the progression of LUAD remain largely unknown. The present bioinformatics analysis reported that FAM83A and FAM83A-AS1 were upregulated in LUAD tissues and associated with prognosis in patients with LUAD. The purpose of the current study was to investigate the role of FAM83A and its antisense long non-coding (lnc)RNA FAM83A-AS1 in LUAD. Gene Expression Profiling Interactive Analysis was used to screen for potential oncogenes in LUAD and to analyze the clinical significance of FAM83A and FAM83A-AS1. Small interfering RNAs were constructed and transfected into LUAD cells to knock down the expression of FAM83A and FAM83A-AS1. EdU, Cell Counting Kit-8, Transwell and Matrigel assays were performed to detect the proliferation, migration and invasion of LUAD cells. The interaction between FAM83A-AS1, microRNA (miR)-495-3p and FAM83A was explored using a luciferase reporter assay. FAM83A and FAM83A-AS1 were both overexpressed in LUAD tissues compared with adjacent normal tissues. High expression of FAM83A and FAM83A-AS1 predicted worse survival and more advanced clinical stage. Knockdown of FAM83A or FAM83A-AS1 could inhibit the proliferation, migration and invasion of LUAD cells. Moreover, lncRNA FAM83A-AS1 regulated the expression of FAM83A by functioning as competing endogenous RNA for miR-495-3p. These results implicated that FAM83A and FAM83A-AS1 both played oncogenic roles in LUAD and FAM83A-AS1 could regulate the expression of FAM83A by sponging miR-495-3p. The study revealed a novel regulatory mechanism of tumor development in LUAD and FAM83A and FAM83A-AS1 may be novel biomarkers and therapeutic targets for LUAD.
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http://dx.doi.org/10.3892/ol.2021.12558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905536PMC
April 2021

TGF-β signaling and microRNA cross-talk regulates abdominal aortic aneurysm progression.

Clin Chim Acta 2021 Apr 31;515:90-95. Epub 2020 Dec 31.

Pathophysiology Department, Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, University of South China, Hengyang, Hunan 421001, PR China. Electronic address:

Abdominal aortic aneurysms (AAA) are permanent and irreversible local dilatations of the abdominal aortic wall. Recent data indicate that the transforming growth factor-beta (TGF-β) signaling pathway exerts a protective effect on the development of AAA. Some dysregulated microRNAs (miRNA) also appear involved in the expansion of AAA and miRNA-based therapeutics have been shown to effectively inhibit this process. New evidence has revealed that TGF-β signaling and miRNA interaction may of physiologic and pathophysiologic significance including the progression of AAA. As such, miRNA that regulate TGF-β signaling may hold promise as potential therapeutic targets. This review explores potential crosstalk between TGF-β signaling and miRNA in AAA in order improve our understanding of this pathology and explore development of potential therapeutic targets.
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http://dx.doi.org/10.1016/j.cca.2020.12.031DOI Listing
April 2021

A validated mouse model capable of recapitulating the protective effects of female sex hormones on ascending aortic aneurysms and dissections (AADs).

Physiol Rep 2020 11;8(22):e14631

Division of Vascular Surgery and Endovascular Therapy, University of Florida College of Medicine, Gainesville, FL, USA.

Fewer females develop AADs (ascending aortic aneurysms and dissections) and the reasons for this protection remain poorly understood. The present study seeks to develop a mouse model that may be utilized to address this sexual dimorphism. Adult normolipidemic mice were challenged with BAPN (β-aminopropionitrile), AngII (angiotensin II), or BAPN + AngII. An initial protocol optimization found that 0.2% BAPN in drinking water plus AngII-infusion at 1,000 ng kg  min produced favorable rates of AAD rupture (~50%) and dilation (~40%) in 28 days. Using these dosages, further experiments revealed that BAPN is toxic to naïve mature aortas and it acted synergistically with AngII to promote aortic tears and dissections. BAPN + AngII provoked early infiltration of myeloid cells and subsequent recruitment of lymphoid cells to the aortic wall. AADs established with BAPN + AngII, but not AngII alone, continued to expand after the cessation of AngII-infusion. This indefinite growth precipitated a 61% increase in the AAD diameter in 56 days. More importantly, with the optimized protocol, significant differences in AAD dilation (p = .012) and medial degeneration (p = .036) were detected between male and female mice. Treatment of ovariectomized mice with estradiol protected AAD formation (p = .014). In summary, this study developed a powerful mouse AAD model that can be used to study the sexual dimorphism in AAD formation.
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http://dx.doi.org/10.14814/phy2.14631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690909PMC
November 2020

Asia-Pacific Consensus Statement on the Management of Peripheral Artery Disease: A Report from the Asian Pacific Society of Atherosclerosis and Vascular Disease Asia-Pacific Peripheral Artery Disease Consensus Statement Project Committee.

J Atheroscler Thromb 2020 Aug 4;27(8):809-907. Epub 2020 Jul 4.

Department of Clinical Epidemiology, University of the Philippines College of Medicine.

Background: Peripheral artery disease (PAD) is the most underdiagnosed, underestimated and undertreated of the atherosclerotic vascular diseases despite its poor prognosis. There may be racial or contextual differences in the Asia-Pacific region as to epidemiology, availability of diagnostic and therapeutic modalities, and even patient treatment response. The Asian Pacific Society of Atherosclerosis and Vascular Diseases (APSAVD) thus coordinated the development of an Asia-Pacific Consensus Statement (APCS) on the Management of PAD.

Objectives: The APSAVD aimed to accomplish the following: 1) determine the applicability of the 2016 AHA/ACC guidelines on the Management of Patients with Lower Extremity Peripheral Artery Disease to the Asia-Pacific region; 2) review Asia-Pacific literature; and 3) increase the awareness of PAD.

Methodology: A Steering Committee was organized to oversee development of the APCS, appoint a Technical Working Group (TWG) and Consensus Panel (CP). The TWG appraised the relevance of the 2016 AHA/ACC PAD Guideline and proposed recommendations which were reviewed by the CP using a modified Delphi technique.

Results: A total of 91 recommendations were generated covering history and physical examination, diagnosis, and treatment of PAD-3 new recommendations, 31 adaptations and 57 adopted statements. This Asia-Pacific Consensus Statement on the Management of PAD constitutes the first for the Asia-Pacific Region. It is intended for use by health practitioners involved in preventing, diagnosing and treating patients with PAD and ultimately the patients and their families themselves.
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http://dx.doi.org/10.5551/jat.53660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458790PMC
August 2020

CircRNAs: A new perspective of biomarkers in the nervous system.

Biomed Pharmacother 2020 Aug 29;128:110251. Epub 2020 May 29.

Hengyang Medical School, Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, University of South China, Hengyang, 421001, China. Electronic address:

Circular RNAs (circRNAs) are a class of newly-identified non-coding RNA that lack 5' (cap) and 3' (polyadenylation) ends and are linked by a covalent bond to form a closed loop structure. In comparison to linear RNAs, circRNAs are more resistant to exonuclease RNase R-mediated degradation with a much stronger stability due to the absence of 3' terminals. Consequently, the extraordinary nature of circRNAs enables it to be potentially used as a biomarker and gene targeting. Similarly, circRNAs can play a significant regulatory role in gene expression where it can indirectly regulate the expression of the downstream target genes of microRNAs (miRNAs) by miRNA sponges. The aim of this review is to highlight the function of circRNAs as well as their vital roles in the central nervous system (CNS) regulation and neurological diseases.
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http://dx.doi.org/10.1016/j.biopha.2020.110251DOI Listing
August 2020

Long non-coding RNA linc00665 interacts with YB-1 and promotes angiogenesis in lung adenocarcinoma.

Biochem Biophys Res Commun 2020 06 15;527(2):545-552. Epub 2020 May 15.

Department of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210000, China; Department of Cardiothoracic Surgery, Jinling Hospital, Southeast University, Nanjing, 210000, China; Department of Cardiothoracic Surgery, Jinling Hospital, Bengbu Medical College, Anhui, 233030, China; Department of Cardiothoracic Surgery, Jinling Hospital, Nanjing Medical University, Nanjing, 210000, China. Electronic address:

Angiogenesis is a core hallmark of advanced cancers, especially in lung adenocarcinoma (LUAD). However, the underlying functions and mechanisms of lncRNAs in tumor angiogenesis remain largely unknown. Here we found that linc00665 depletion could markedly depressed proliferation and capillary tube formation of HUVECs in vitro. Mechanistically, linc00665 directly interacted with YB-1 protein, enhanced its stability through inhibiting ubiquitination-dependent proteolysis and stimulated its nuclear translocation in LUAD cells. The accumulated nuclear YB-1 activated expression of ANGPT4, ANGPTL3 and VEGFA by binding to their promoters, contributing to tumor-related angiogenesis in vitro and in vivo. Collectively, we conclude that linc00665 induces tumor-related angiogenesis in LUAD by directly interacting with YB-1 and activating YB-1-ANGPT4/ANGPTL3/VEGFA axis, which provides promising anti-angiogenic targets for cancer therapy.
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http://dx.doi.org/10.1016/j.bbrc.2020.04.108DOI Listing
June 2020

Three Musketeers for Lowering Cholesterol: Statins, Ezetimibe and Evolocumab.

Curr Med Chem 2021 ;28(5):1025-1041

Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China.

Coronary heart disease (CHD) is closely related to hypercholesterolemia, and lowering serum cholesterol is currently the most important strategy in reducing CHD. In humans, the serum cholesterol level is determined mainly by three metabolic pathways, namely, dietary cholesterol intake, cholesterol synthesis, and cholesterol degradation in vivo. An intervention that targets the key molecules in the three pathways is an important strategy in lowering serum lipids. Statins inhibit 3-hydroxyl-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) to reduce low-density lipoprotein (LDL) by about 20% to 45%. However, up to 15% of patients cannot tolerate the potential side effects of high statin dosages, and several patients also still do not reach their optimal LDL goals after being treated with statins. Ezetimibe inhibits cholesterol absorption by targeting the Niemann-Pick C1-like 1 protein (NPC1L1), which is related to cholesterol absorption in the intestines. Ezetimibe lowers LDL by about 18% when used alone and by an additional 25% when combined with statin therapy. The proprotein convertase subtilisin/kexin type 9 (PCSK9) increases hepatic LDLR degradation, thereby reducing the liver's ability to remove LDL, which can lead to hypercholesterolemia. Evolocumab, which is a PCSK9 monoclonal antibody, can reduce LDL from baseline by 53% to 56%. The three drugs exert lipid-lowering effects by regulating the three key pathways in lipid metabolism. Combining any with the two other drugs on the basis of statin treatment has improved the lipid-lowering effect. Whether the combination of the three musketeers will reduce the side effects of monotherapy and achieve the lipid-lowering effect should be studied further in the future.
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http://dx.doi.org/10.2174/0929867327666200505091738DOI Listing
April 2021

Synaptotagmin 12 (SYT12) Gene Expression Promotes Cell Proliferation and Progression of Lung Adenocarcinoma and Involves the Phosphoinositide 3-Kinase (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) Pathway.

Med Sci Monit 2020 Feb 28;26:e920351. Epub 2020 Feb 28.

Department of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China (mainland).

BACKGROUND This study aimed to use bioinformatics analysis to compare data from tissue microarrays from patients with lung adenocarcinoma (LUAD) and normal lung tissue, and human lung adenocarcinoma cells with normal lung epithelial cells in vitro to investigate the role of synaptotagmin 12 (SYT12) gene expression in LUAD. MATERIAL AND METHODS Human lung adenocarcinoma cell lines (A549, SPC-A-1, H1299, H1975, and PC9) and the normal HBE cell line were compared, and tumor xenografts were developed in mice. The Cancer Genome Atlas (TCGA) tissue microarray data were used to compare SYT12 expression and overall survival (OS). The in vivo and in vitro effects of down-regulation and upregulation of SYT12 were studied using short-interfering RNA (si-RNA) and overexpression plasmids, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway analysis, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and Western blot investigated the molecular mechanisms of SYT12 expression in LUAD. RESULTS SYT12 expression was increased in tissues from patients with LUAD from TCGA and was associated with advanced tumor stage and reduced prognosis. Knockdown of SYT12 suppressed the proliferation and migration of LUAD cells, and upregulation of SYT12 increased the proliferation and migration of LUAD cells in vitro. Phosphorylation of PIK3R3 activated the PI3K/AKT/mTOR pathway. In the mouse xenograft model, expression of SYT12 increased the volume and weight of the xenograft tumors. CONCLUSIONS Bioinformatics analysis, human LUAD cells, and mouse xenograft studies showed that SYT12 acted as a possible oncogene by phosphorylation of PIK3R3 to activate the PI3K/AKT/mTOR signaling pathway.
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http://dx.doi.org/10.12659/MSM.920351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063850PMC
February 2020

The role of IL-1β in aortic aneurysm.

Clin Chim Acta 2020 May 13;504:7-14. Epub 2020 Jan 13.

Pathophysiology Department, Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, University of South China, Hengyang City, Hunan Province 421001, PR China. Electronic address:

Interleukin-1β (IL-1β) is a vital cytokine that plays an important role in regulating immune responses to infectious challenges and sterile insults. In addition, two endogenous inhibitors of functional receptor binding, IL-1 receptor antagonist (IL-1Ra), complete the family. To gain biological activity, IL-1β requires processing by the protease caspase-1 and activation of inflammasomes. Numerous clinical association studies and experimental approaches have implicated members of the IL-1 family, their receptors, or components of the processing machinery in the underlying processes of cardiovascular diseases. Here, we summarize the current state of knowledge regarding the pro-inflammatory and disease-modulating role of the IL-1 family in aneurysm. We discuss clinical evidence, signalling pathway, and mechanism of action and last, lend a perspective on currently developing therapeutic strategies involving IL-1β in aneurysm.
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http://dx.doi.org/10.1016/j.cca.2020.01.007DOI Listing
May 2020

Outcomes Of Chimney Technique For Aortic Arch Diseases: A Single-Center Experience With 226 Cases.

Clin Interv Aging 2019 25;14:1829-1840. Epub 2019 Oct 25.

Institute of Cardiovascular Disease and Key Laboratory for Arteriosclerology of Hunan Province, Hengyang Medical School, University of South China, Hengyang, Hunan, People's Republic of China.

Purpose: The goal of present study is to document our single-center experience with chimney technique for aortic arch diseases.

Patients And Methods: From August 2012 to October 2017, 226 patients (mean age 54±12 years; 197 men) with aortic arch diseases underwent thoracic endovascular aortic repair combined with chimney stents. The aortic stent-grafts were deployed in zone 0 (n=22), zone 1 (n=13), or zone 2 (n=191).

Results: The technical success rate was 84% (189/226) and immediate type Ia endoleak (ELIa) happened in 37 (16%) patients. The 30-day mortality and morbidity rates were 2% (4/226) and 4% (8/226), respectively. Major adverse events include four major strokes, three spinal cord ischemia and one aortic rupture in the early-term. The clinical and imaging follow-up rates were 98% (218/222) and 78% (173/222), respectively. The average lengths of clinical and imaging follow-up were 22±16 months and 20±15 months, respectively. Chimney stent obstructions in left subclavian arteries were recorded in six (3%) patients. During follow-up, five patients died (2%) and two major strokes occurred (1%). One patient (0.5%) underwent reintervention.

Conclusion: The current study documented that the chimney technique is effective and safe for treating aortic arch diseases in different aortic zones. Cautions are needed to assess the permanency of chimney stent and to reduce the immediate ELIa rate.
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http://dx.doi.org/10.2147/CIA.S222948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818674PMC
March 2020

The TGF-β pathway plays a key role in aortic aneurysms.

Clin Chim Acta 2020 Feb 9;501:222-228. Epub 2019 Nov 9.

Pathophysiology Department, Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, University of South China, Hengyang City, Hunan Province 421001, PR China. Electronic address:

Aortic dissection and aortic aneurysms are currently among the most high-risk cardiovascular diseases due to their rapid onset and high mortality. Although aneurysm research has been extensive, the pathogenesis remains unknown. Studies have found that the TGF-β/Smad pathway and aneurysm formation appear linked. For example, the TGF-β signaling pathway was significantly activated in aneurysm development and aortic dissection. Aneurysms are not, however, mitigated following knockdown of TGF-β signaling pathway-related genes. Incidence and mortality rate of ruptured thoracic aneurysms increase with the down-regulation of the classical TGF-β signaling pathway. In this review, we summarize recent findings and evaluate the differential role of classical and non-classical TGF-β pathways on aortic aneurysm. It is postulated that the TGF-β signaling pathway is necessary to maintain vascular function, but over-activation will promote aneurysms whereas over-inhibition will lead to bypass pathway over-activation and promote aneurysm occurrence.
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http://dx.doi.org/10.1016/j.cca.2019.10.042DOI Listing
February 2020

eIF2α promotes vascular remodeling via autophagy in monocrotaline-induced pulmonary arterial hypertension rats.

Drug Des Devel Ther 2019 13;13:2799-2809. Epub 2019 Aug 13.

Key Laboratory for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, University of South China, Hengyang 421001, Hunan, People's Republic of China.

Purpose: Eukaryotic initiation factor 2α (eIF2α) plays important roles in the proliferation and survival of pulmonary artery smooth muscle cells (PASMCs) in animal hypoxia-induced pulmonary hypertension models. However, the underlying mechanism remains unknown at large. Autophagy has been reported to play a key role in the vascular remodeling in pulmonary arterial hypertension (PAH). The purposes of this study are to determine the functions of eIF2α and autophagy in the vascular remodeling of the monocrotaline-induced PAH rats and to clarify the correlation between eIF2α and autophagy.

Methods: We established a rat model of monocrotaline-induced PAH, and we established a cell model of platelet derived growth factor (PDGF)-induced PASMCs proliferation. The vascular morphology and the expression of eIF2α, LC3B, and p62 were assessed in the pulmonary arterial tissue of Sprague-Dawleyrats and PDGF-induced PASMCs.

Results: Autophagy was significantly active in monocrotaline model group (MCT)-induced PAH rats, which obviously promotes vascular remodeling in MCT-induced PAH rats. Furthermore, the proliferation of PASMCs was induced by PDGF in vitro. The expression of LC3B, eIF2α was increased in the PDGF-induced PASMCs proliferation, and the expression of p62 was reduced in the PDGF-induced PASMCs proliferation. Moreover, eIF2α siRNA downregulated the expression of eIF2α and LC3B, and upregulated the expression of p62 in PDGF-induced PASMCs proliferation. eIF2α siRNA inhibited the PDGF-induced PASMCs proliferation. Finally, chloroquine can upregulate the protein expression of LC3B and p62, it also can inhibit proliferation in PDGF-induced PASMCs.

Conclusion: Based on these observations, we conclude that eIF2α promotes the proliferation of PASMCs and vascular remodeling in monocrotaline-induced PAH rats through accelerating autophagy pathway.
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http://dx.doi.org/10.2147/DDDT.S213817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698179PMC
April 2020

Involvement of miR-145 in the development of aortic dissection via inducing proliferation, migration, and apoptosis of vascular smooth muscle cells.

J Clin Lab Anal 2020 Jan 6;34(1):e23028. Epub 2019 Sep 6.

Institute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan Province, Hengyang Medical School, University of South China, Hengyang, China.

Aim: The current study aimed to examine miR-145's contribution to thoracic aortic dissection (AD) development by modulating the biological functions of vascular smooth muscle cells (VSMCs).

Methods: The concentration of circulating miR-145 was determined in patients with AD and healthy controls using quantitative polymerase chain reaction (qPCR). Aortic specimens were obtained from both individuals with Stanford type A AD undergoing surgical treatment and deceased organ donors (serving as controls) whose causes of death were nonvascular diseases. Then, qPCR and fluorescence in situ hybridization were applied to assess miR-145 amounts and location, respectively. Furthermore, qPCR and immunoblot were employed to determine SMAD3 (the target gene of miR-145, involved in the TGF-β pathway) amounts at the gene and protein levels, respectively. Moreover, in vitro transfection of VSMCs with miR-145 mimics or inhibitors was conducted. Finally, the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Transwell assay and flow cytometry were employed for detecting VSMC proliferation, migration, and apoptosis, respectively.

Results: The amounts of miR-145 in plasma and aortic specimens were markedly reduced in the AD group in comparison with control values (P < .05). miR-145 was mostly located in VSMCs. Proliferation and apoptosis of VSMCs were significantly induced in vitro by the downregulation of miR-145. Also, miR-145 modulated SMAD3 expression.

Conclusions: miR-145 was found to be downregulated in patients with AD, which induced the proliferation, migration, and apoptosis of VSMCs by targeting SMAD3. This suggested the involvement of miR-145 in the pathogenesis of AD.
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http://dx.doi.org/10.1002/jcla.23028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977357PMC
January 2020

Administration of metformin alleviates atherosclerosis by promoting H2S production via regulating CSE expression.

J Cell Physiol 2020 03 23;235(3):2102-2112. Epub 2019 Jul 23.

Department of Cardiology, Beijing Hospital of Traditional Chinese Medicine, Beijing, China.

The therapeutic effect of metformin (Met) on atherosclerosis was studied here. Effects of methionine and Met on the induction of inflammatory response and H S expression in peritoneal macrophages were evaluated. Enzyme-linked immunosorbent assay, immunohistochemistry assay, western blot, and quantitative reverse transcription polymerase chain reaction were conducted to observe the levels of cystathionine γ-lyase (CSE), DNA methyltransferases 1 (DNMT1), DNMT3a, DNMT3b, tumor necrosis factor (TNF- α), interleukin 1b (IL-1β), and hydrogen sulfide (H S). Luciferase and bisulfite sequencing assays were also utilized to evaluate the CSE promoter activity as well as the methylation status of CSE in transfected cells. Methionine significantly elevated Hcy, TNF-a, H S, and IL-1β expression while decreasing the level of CSE in C57BL/6 mice. In contrary, co-treatment with Methionine and Met reduced the detrimental effect of Methionine. Homocysteine (Hcy) decreased H S expression while promoting the synthesis of IL-1β and TNF-α in THP-1 and raw264.7 cells. Treatment of THP-1 and raw264.7 cells with methionine and Met reduced the activity of methionine in dose dependently. Moreover, Hcy increased the expression of DNMT and elevated the level of methylation in the CSE promoter, whereas the co-treatment with methionine and Met attenuated the effects of Hcy. Methionine significantly decreased plasma level of CSE while increasing the severity of inflammatory responses and plasma level of Hcy, which in turn suppressed H S synthesis and enhanced DNA hypermethylation of CSE promoter to promote the pathogenesis of atherosclerosis. In contrary, co-treatment with methionine and Met reduced the detrimental effect of methionine.
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http://dx.doi.org/10.1002/jcp.29112DOI Listing
March 2020

TRIM65 E3 ligase targets VCAM-1 degradation to limit LPS-induced lung inflammation.

J Mol Cell Biol 2020 04;12(3):190-201

Department of Biomedical Science, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA.

Although the adhesion molecules-mediated leukocyte adherence and infiltration into tissues is an important step of inflammation, the post-translational regulation of these proteins on the endothelial cells is poorly understood. Here, we report that TRIM65, an ubiquitin E3 ligase of tripartite protein family, selectively targets vascular cell adhesion molecule 1 (VCAM-1) and promotes its ubiquitination and degradation, by which it critically controls the duration and magnitude of sepsis-induced pulmonary inflammation. TRIM65 is constitutively expressed in human vascular endothelial cells. During TNFα-induced endothelial activation, the protein levels of TRIM65 and VCAM-1 are inversely correlated. Expression of wild-type TRIM65, but not expression of a TRIM65 mutant that lacks E3 ubiquitin ligase function in endothelial cells, promotes VCAM-1 ubiquitination and degradation, whereas small interference RNA-mediated knockdown of TRIM65 attenuates VCAM-1 protein degradation. Further experiments show that TRIM65 directly interacts with VCAM-1 protein and directs its polyubiquitination, by which TRIM65 controls monocyte adherence and infiltration into tissues during inflammation. Importantly, TRIM65-deficient mice are more sensitive to lipopolysaccharide-induced death, due to sustained and severe pulmonary inflammation. Taken together, our studies suggest that TRIM65-mediated degradation of VCAM-1 represents a potential mechanism that controls the duration and magnitude of inflammation.
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http://dx.doi.org/10.1093/jmcb/mjz077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181722PMC
April 2020

Femtosecond laser enabled selective micro-holes drilling on the multicore-fiber facet for displacement sensor application.

Opt Express 2019 Apr;27(8):10777-10786

We experimentally demonstrate a femtosecond laser enabled selective micro-holes drilling technique on the multicore-fiber facet. The precise position of individual cores at the seven-core fiber facet is initially locked by the image processing algorithm, and then six micro-holes are successfully fabricated after the pulse energy of femtosecond laser is optimized. Meanwhile, the use of fabricated seven-core fiber for the application of reflective intensity-modulated fiber optics displacement sensor (RIM-FODS) is comprehensively investigated. By using the beam propagation method (BPM), we theoretically investigate the effect of micro-hole depth on the RIM-FODS performance, in terms of both dead zone and measurement range. We identify that, with the increase of micro-hole depth, the dead zone range can be substantially reduced at the expense of measurement range reduction. However, multiple micro-holes with a successive depth difference can overcome such problem. When the micro-holes with depths of 5, 10, 15, 20, 25, 30 μm are fabricated on the seven-core fiber facet, and the dead zone range can be substantially reduced from 150 μm to 20 μm, together with an extension of measurement range from 250 μm to 400 μm.
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http://dx.doi.org/10.1364/OE.27.010777DOI Listing
April 2019

Rice qGL3/OsPPKL1 Functions with the GSK3/SHAGGY-Like Kinase OsGSK3 to Modulate Brassinosteroid Signaling.

Plant Cell 2019 05 28;31(5):1077-1093. Epub 2019 Mar 28.

State Key Laboratory of Crop Genetics and Germplasm Enhancement, College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China

Brassinosteroids (BRs) are steroid hormones that play essential roles in plant growth and development. We previously cloned , a major quantitative trait locus regulating grain length in rice (). The var N411 has extra-large grains compared with the var 9311, and the recessive allele from N411 contributes positively to grain length. encodes a putative protein phosphatase with Kelch-like repeat domains, an ortholog of Arabidopsis () SUPPRESSOR1 (BSU1). BSU1 positively regulates BR signaling, while overexpression of induced BR loss-of-function phenotypes. Both qGL3 and qGL3 physically interact with the rice glycogen synthase kinase 3 (GSK3)/SHAGGY-like kinase 3 (OsGSK3), an ortholog of Arabidopsis BR INSENSITIVE2 (BIN2). qGL3 dephosphorylates OsGSK3, but qGL3 lacks this activity. Knocking out enhances BR signaling and induces nuclear localization of BRASSINAZOLE RESISTANT1 (OsBZR1). Unlike the dephosphorylation of BIN2 (which leads to protein degradation) in Arabidopsis, qGL3 dephosphorylates and stabilizes OsGSK3 in rice. These results demonstrate that qGL3 suppresses BR signaling by regulating the phosphorylation and stability of OsGSK3, which modulates OsBZR1 phosphorylation and subcellular distribution. Our study clarifies the role of qGL3 in the regulation of grain length and provides insight into BR signaling, including the differences between rice and Arabidopsis.
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http://dx.doi.org/10.1105/tpc.18.00836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533024PMC
May 2019

Long non-coding RNA linc00665 promotes lung adenocarcinoma progression and functions as ceRNA to regulate AKR1B10-ERK signaling by sponging miR-98.

Cell Death Dis 2019 01 28;10(2):84. Epub 2019 Jan 28.

Department of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, 210000, Nanjing, China.

Long non-coding RNAs (lncRNAs) are frequently dysregulated in multiple malignancies, demonstrating their potential oncogenic or tumor-suppressive roles in tumorigenesis. Herein, we reported the identification of a novel lncRNA, linc00665 (ENST00000590622), which was markedly upregulated in lung adenocarcinoma (LUAD) tissues and might serve as an independent predictor for poor prognosis. Functional assays indicated that linc00665 reinforced LUAD cell proliferation and metastasis in vitro and in vivo. Mechanistically, transcription factor SP1 induced the transcription of linc00665 in LUAD cells, which exerted its oncogenic role by functioning as competing endogenous RNA (ceRNA) for miR-98 and subsequently activating downstream AKR1B10-ERK signaling pathway. Together, our study elucidates oncogenic roles of linc00665-miR98-AKR1B10 axis in LUAD tumorigenesis, which may serve as potential diagnostic biomarkers and therapeutic targets.
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http://dx.doi.org/10.1038/s41419-019-1361-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349882PMC
January 2019

OxLDL induces vascular endothelial cell pyroptosis through miR-125a-5p/TET2 pathway.

J Cell Physiol 2019 05 28;234(5):7475-7491. Epub 2018 Oct 28.

Key Lab for Atherosclerology of Hunan Province, Institute of Cardiovascular Disease, University of South China, Hengyang, China.

Pyroptosis participates in the formation and development of atherosclerosis (As) by promoting inflammatory factor release and is closely related to the stability of atherosclerotic plaque. MicroRNAs can regulate the expression of target genes at the posttranscriptional level. Previous studies have shown that miR-125a-5p increases in hyperlipidemic-hyperglycemic conditions and is involved in apoptosis, but its specific role in pyroptosis and As remains unclear. We propose that miR-125a-5p may be implicated in oxidized low-density lipoprotein (oxLDL)-induced vascular endothelial cells (VECs) pyroptosis and therefore conducted the current study. We observed that miR-125a-5p can inhibit tet methylcytosine dioxygenase 2 (TET2) expression at the posttranscription level, resulting in abnormal DNA methylation, mitochondrial dysfunction, and increased reactive oxygen species production, activated nuclear factor-κB that induces activation of inflammasome and maturation, release of proinflammatory cytokines interleukin (IL)-1β and IL-18, and pyroptosis. Given the role of VECs in vascular physiology, oxLDL-induced VEC pyroptosis may promote the development of As. Our current study reveals a novel pathway associated with pyroptosis program regulation, which comprises miR-125a-5p and TET2 in VECs. Modulation of their expression levels may serve as a potential target for therapeutic strategies of As.
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http://dx.doi.org/10.1002/jcp.27509DOI Listing
May 2019

Probiotics combined with aminosalicylic acid affiliates remission of ulcerative colitis: a meta-analysis of randomized controlled trial.

Biosci Rep 2019 01 18;39(1). Epub 2019 Jan 18.

Institute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan Province, University of South China, Hengyang, Hunan Province 421001, People's Republic of China

We conducted a meta-analysis to evaluate the effect of probiotic combined with aminosalicylic on induction remission maintenance treatment of ulcerative colitis (UC). We conducted systematic searches in several Chinese and English databases from inception to June 2018, screening randomized controlled trials about effect of probiotics combined with aminosalicylic acid on UC. The evaluation indicator was the rate of remission. The relative risk (RR) and 95% confidence interval (CI) were calculated. A total of 27 studies with 1942 patients were included. The results indicated that the remission rate was significantly higher in the group using probiotics combined with aminosalicylic acid than that in the group using aminosalicylic acid alone (RR = 1.40, 95% CI: 1.27-1.53, =0.000). The subgroup analysis indicated that probiotics combined with aminosalicylic acid can significantly elevate the remission rate in both mild to moderate (RR = 1.33, 95% CI: 1.16-1.54, =0.000) and active stage (RR = 1.40, 95% CI: 1.27-1.64, =0.000) UC. In different number of bacterium, drug types and treatment periods, the combination with probiotics can significantly increase the remission rate UC. The funnel plot shows slight publication bias. Probiotics in conjunction with aminosalicylic can obviously increase the clinical remission rate of activity UC than drug alone. There was no significant difference between combined with mesalazine group and salicylazosulfapyridine group.
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http://dx.doi.org/10.1042/BSR20180943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340951PMC
January 2019

Brown Adipocyte-Specific PPARγ (Peroxisome Proliferator-Activated Receptor γ) Deletion Impairs Perivascular Adipose Tissue Development and Enhances Atherosclerosis in Mice.

Arterioscler Thromb Vasc Biol 2018 08;38(8):1738-1747

Department of Internal Medicine, Frankel Cardiovascular Center (W.X., X.Z., L.V., O.R., M.T.G.-B., Y.G., Y.F., T.Z., J.Z., L.C.).

Objective- Perivascular adipose tissue (PVAT) contributes to vascular homeostasis by producing paracrine factors. Previously, we reported that selective deletion of PPARγ (peroxisome proliferator-activated receptor γ) in vascular smooth muscle cells resulted in concurrent loss of PVAT and enhanced atherosclerosis in mice. To address the causal relationship between loss of PVAT and atherosclerosis, we used BA-PPARγ-KO (brown adipocyte-specific PPARγ knockout) mice. Approach and Results- Deletion of PPARγ in brown adipocytes did not affect PPARγ in white adipocytes or vascular smooth muscle cells or PPARα and PPARδ expression in brown adipocytes. However, development of PVAT and interscapular brown adipose tissue was remarkably impaired, associated with reduced expression of genes encoding lipogenic enzymes in the BA-PPARγ-KO mice. Thermogenesis in brown adipose tissue was significantly impaired with reduced expression of thermogenesis genes in brown adipose tissue and compensatory increase in subcutaneous and gonadal white adipose tissues. Remarkably, basal expression of inflammatory genes and macrophage infiltration in PVAT and brown adipose tissue were significantly increased in the BA-PPARγ-KO mice. BA-PPARγ-KO mice were crossbred with ApoE KO (apolipoprotein E knockout) mice to investigate the development of atherosclerosis. Flow cytometry analysis confirmed increased systemic and PVAT inflammation. Consequently, atherosclerotic lesions were significantly increased in mice with impaired PVAT development, thus indicating that the lack of normal PVAT is sufficient to drive increased atherosclerosis. Conclusions- PPARγ is required for functional PVAT development. PPARγ deficiency in PVAT, while still expressed in vascular smooth muscle cell, enhances atherosclerosis and results in vascular and systemic inflammation, providing new insights on the specific roles of PVAT in atherosclerosis and cardiovascular disease at large.
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http://dx.doi.org/10.1161/ATVBAHA.118.311367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202167PMC
August 2018

Pharmacological inhibition of MALT1 protease activity suppresses endothelial activation via enhancing MCPIP1 expression.

Cell Signal 2018 Oct 18;50:1-8. Epub 2018 Jun 18.

Department of Biomedical Science and Shock/Trauma Research Center, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA. Electronic address:

Mucosa associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is not only an intracellular signaling scaffold protein but also a paracaspase that plays a key role in the signal transduction and cellular activation of lymphocytes and macrophages. However, its role in endothelial cells remains unknown. Here we report that pharmacological inhibition of MALT1 protease activity strongly suppresses endothelial activation via enhancing MCPIP1 expression. Treatment with MALT1 protease inhibitors selectively inhibited TNFα-induced VCAM-1 expression in HUVECs and LPS-induced VCAM-1 expression in mice. In addition, Inhibition of MALT1 protease activity also significantly inhibited TNFα-induced adhesion of THP-1 monocytic cells to HUVECs. To explore the mechanisms, MALT1 inhibitors does not affect the activation of NF-κB signaling pathway in HUVEC. However, they can stabilize MCPIP1 protein and significantly enhance MCPIP1 protein level in endothelial cells. These results suggest that MALT1 paracaspase also targets MCPIP1 and degrade MCPIP1 protein in endothelial cells similar as it does in immune cells. Taken together, the study suggest inhibition of MALT1 protease activity may represent a new strategy for prevention/therapy of vascular inflammatory diseases such as atherosclerosis.
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http://dx.doi.org/10.1016/j.cellsig.2018.05.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086570PMC
October 2018

Involvement of CGRP-RCP in the caveolin-1/ERK1/2 signal pathway in the static pressure-induced proliferation of vascular smooth muscle cells.

J Cell Physiol 2018 10 9;233(10):6910-6920. Epub 2018 May 9.

Institute of Pharmacy and Pharmacology, Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang, China.

Previous study suggested that the receptor component protein (RCP), one of the components of calcitonin gene-related peptide (CGRP) receptor, plays a multiple role in the cellular signal transduction. The study was designed to investigate whether or not the RCP involved in the regulation of caveolin-1/extracellular signal-regulated kinases-1 and -2 (ERK1/2) signal pathway in the vascular smooth muscle cells (VSMCs) proliferation induced by static pressure. Mouse-derived VSMCs line A10 (A10 VSMCs) was served as project in this experiment. Results showed that the A10 VSMCs viability and proliferating cell nuclear antigen (PCNA) expression which were increased by static pressure were inhibited by pretreatment of CGRP. In like manner, the expressions of the decreased-caveolin-1 and the increased-phosphorylated ERK1/2 (p-ERK1/2) induced by static pressure were significantly reversed by pretreatment of CGRP, respectively. Meanwhile, the expression of RCP was up-regulated by the static pressure. Silence of RCP gene with the small interrupt RNA (siRNA) not only significantly increased A10 VSMC proliferation but also increased the expression of p-ERK1/2 in response to static pressure. When treatment of A10 VSMCs with 120-mmHg static pressure for different time, however, the protein band of caveolin-1 and RCP was the least at time point of 10 min, but the p-ERK1/2 expression was the most maximum. In conclusion, RCP maybe involved in the static pressure-induced A10 VSMCs proliferation by regulation of caveolin-1/ERK1/2 signal pathway.
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http://dx.doi.org/10.1002/jcp.26582DOI Listing
October 2018

Bmal1 in Perivascular Adipose Tissue Regulates Resting-Phase Blood Pressure Through Transcriptional Regulation of Angiotensinogen.

Circulation 2018 07 25;138(1):67-79. Epub 2018 Jan 25.

Cardiovascular Center, Department of Internal Medicine (L.C., X.Z., Y.F., Y.G., M.G.B., J.Z., Y.E.C.)

Background: The perivascular adipose tissue (PVAT) surrounding vessels constitutes a distinct functional integral layer of the vasculature required to preserve vascular tone under physiological conditions. However, there is little information on the relationship between PVAT and blood pressure regulation, including its potential contributions to circadian blood pressure variation.

Methods: Using unique brown adipocyte-specific aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) and angiotensinogen knockout mice, we determined the vasoactivity of homogenized PVAT in aortic rings and how brown adipocyte peripheral expression of Bmal1 and angiotensinogen in PVAT regulates the amplitude of diurnal change in blood pressure in mice.

Results: We uncovered a peripheral clock in PVAT and demonstrated that loss of Bmal1 in PVAT reduces blood pressure in mice during the resting phase, leading to a superdipper phenotype. PVAT extracts from wild-type mice significantly induced contractility of isolated aortic rings in vitro in an endothelium-independent manner. This property was impaired in PVAT from brown adipocyte-selective Bmal1-deficient (BA-Bmal1-KO) mice. The PVAT contractile properties were mediated by local angiotensin II, operating through angiotensin II type 1 receptor-dependent signaling in the isolated vessels and linked to PVAT circadian regulation of angiotensinogen. Indeed, angiotensinogen mRNA and angiotensin II levels in PVAT of BA-Bmal1-KO mice were significantly reduced. Systemic infusion of angiotensin II, in turn, reduced Bmal1 expression in PVAT while eliminating the hypotensive phenotype during the resting phase in BA-Bmal1-KO mice. Angiotensinogen, highly expressed in PVAT, shows circadian expression in PVAT, and selective deletion of angiotensinogen in brown adipocytes recapitulates the phenotype of selective deletion of Bmal1 in brown adipocytes. Furthermore, angiotensinogen is a transcriptional target of Bmal1 in PVAT.

Conclusions: These data indicate that local Bmal1 in PVAT regulates angiotensinogen expression and the ensuing increase in angiotensin II, which acts on smooth muscle cells in the vessel walls to regulate vasoactivity and blood pressure in a circadian fashion during the resting phase. These findings will contribute to a better understanding of the cardiovascular complications of circadian disorders, alterations in the circadian dipping phenotype, and cross-talk between systemic and peripheral regulation of blood pressure.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.117.029972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030431PMC
July 2018

Biological functions of Elabela, a novel endogenous ligand of APJ receptor.

J Cell Physiol 2018 09 25;233(9):6472-6482. Epub 2018 Mar 25.

Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, P.R. China.

The G protein-coupled receptor APJ and its cognate ligand, apelin, are widely expressed throughout human body. They are implicated in different key physiological processes such as angiogenesis, cardiovascular functions, fluid homeostasis, and energy metabolism regulation. Recently, a new endogenous peptidic ligand of APJ, named Elabela, has been identified and shown to play a crucial role in embryonic development. In addition, increasing evidences show that Elabela is also intimate associated with a large number of physiological processes in adulthood. However, a comprehensive summary of Elabela has not been reported to date. In this review, we provide an overview of the biological functions of Elabela. Collectively, Elabela, a potential therapeutic peptide, exerts diverse biological functions in both embryos and adult organisms, such as dysontogenesis, self-renewing of human embryonic stem cells, endoderm differentiation, heart morphogenesis, cardiac dyfunctions, blood pressure control, angiogenesis, blood pressure control, regulation of food and water intake, bone formation, and kidney diseases.
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http://dx.doi.org/10.1002/jcp.26492DOI Listing
September 2018

MitoNEET in Perivascular Adipose Tissue Blunts Atherosclerosis under Mild Cold Condition in Mice.

Front Physiol 2017 19;8:1032. Epub 2017 Dec 19.

Cardiovascular Research Center, University of Michigan, Ann Arbor, MI, United States.

Perivascular adipose tissue (PVAT), which surrounds most vessels, is de facto a distinct functional vascular layer actively contributing to vascular function and dysfunction. PVAT contributes to aortic remodeling by producing and releasing a large number of undetermined or less characterized factors that could target endothelial cells and vascular smooth muscle cells, and herein contribute to the maintenance of vessel homeostasis. Loss of PVAT in mice enhances atherosclerosis, but a causal relationship between PVAT and atherosclerosis and the possible underlying mechanisms remain to be addressed. The CDGSH iron sulfur domain 1 protein (referred to as mitoNEET), a mitochondrial outer membrane protein, regulates oxidative capacity and adipose tissue browning. The roles of mitoNEET in PVAT, especially in the development of atherosclerosis, are unknown. The brown adipocyte-specific mitoNEET transgenic mice were subjected to cold environmental stimulus. The metabolic rates and PVAT-dependent thermogenesis were investigated. Additionally, the brown adipocyte-specific mitoNEET transgenic mice were cross-bred with ApoE knockout mice. The ensuing mice were subsequently subjected to cold environmental stimulus and high cholesterol diet challenge for 3 months. The development of atherosclerosis was investigated. Our data show that mitoNEET mRNA was downregulated in PVAT of both peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc1α)- and beta (Pgc1β)-knockout mice which are sensitive to cold. MitoNEET expression was higher in PVAT of wild type mice and increased upon cold stimulus. Transgenic mice with overexpression of mitoNEET in PVAT were cold resistant, and showed increased expression of thermogenic genes. ApoE knockout mice with mitoNEET overexpression in PVAT showed significant downregulation of inflammatory genes and showed reduced atherosclerosis development upon high fat diet feeding when kept in a 16°C environment. mitoNEET in PVAT is associated with PVAT-dependent thermogenesis and prevents atherosclerosis development. The results of this study provide new insights on PVAT and mitoNEET biology and atherosclerosis in cardiovascular diseases.
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http://dx.doi.org/10.3389/fphys.2017.01032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742148PMC
December 2017

Risk factors for neurogenic pulmonary edema in patients with severe hand, foot, and mouth disease: A meta-analysis.

Int J Infect Dis 2017 Dec 29;65:37-43. Epub 2017 Sep 29.

Institute of Cardiovascular Disease and Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang, Hunan, People's Republic of China. Electronic address:

Objective: To investigate the risk factors for neurogenic pulmonary edema (NPE) in patients with severe hand, foot, and mouth disease (HFMD) and to provide evidence for the prevention and treatment of NPE.

Methods: Several databases were searched (from inception to 2017) to identify case-control studies on risk factors for NPE among patients with severe HFMD. Data were analyzed via meta-analysis. The combined odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed-effects and random-effects models, and a sensitivity analysis and evaluation of publication bias was also performed.

Results: A total of 14 studies involving 557 cases (severe HFMD with NPE) and 1450 controls (severe HFMD) were included. Results for the categorical variables were as follows: hyperglycemia (OR 10.25, 95% CI 4.82-21.76), tachycardia (OR 6.21, 95% CI 3.02-12.75), hypertension (OR 3.79, 95% CI 2.90-4.95), respiratory rhythm abnormality (OR 7.86, 95% CI 2.46-25.12), drowsiness (OR 8.11, 95% CI 4.26-15.44), vomiting (OR 8.96, 95% CI 3.83-20.96), limb tremors (OR 8.96, 95% CI 3.83-20.96), atypical rash (OR 4.27, 95% CI 2.83-6.45). No significant publication bias was found for the different factors.

Conclusions: Drowsiness ranks first among risk factors for NPE in children with severe HFMD, followed by vomiting, tachycardia, hypertension, breathing rhythm changes, limb tremors, atypical rash, and hyperglycemia.
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http://dx.doi.org/10.1016/j.ijid.2017.09.020DOI Listing
December 2017

An X-linked Myh11-CreER mouse line resulting from Y to X chromosome-translocation of the Cre allele.

Genesis 2017 09;55(9)

Division of Vascular Surgery and Endovascular Therapy, University of Florida College of Medicine, Gainesville, Florida, 32610.

The Myh11-CreER mouse line (Cre ) has gained increasing application because of its high lineage specificity relative to other Cre drivers targeting smooth muscle cells (SMCs). This Cre allele, however, was initially inserted into the Y chromosome (X/Y ), which excluded its application in female mice. Our group established a Cre colony from male ancestors. Surprisingly, genotype screening identified female carriers that stably transmitted the Cre allele to the following generations. Crossbreeding experiments revealed a pattern of X-linked inheritance for the transgene (k > 1000), indicating that these female carries acquired the Cre allele through a mechanism of Y to X chromosome translocation. Further characterization demonstrated that in hemizygous X/X mice Cre activity was restricted to a subset arterial SMCs, with Cre expression in arteries decreased by 50% compared to X/Y mice. This mosaicism, however, diminished in homozygous X /X mice. In a model of aortic aneurysm induced by a SMC-specific Tgfbr1 deletion, the homozygous X /X Cre driver unmasked the aortic phenotype that is otherwise subclinical when driven by the hemizygous X/X Cre line. In conclusion, the Cre allele carried by this female mouse line is located on the X chromosome and subjected to X-inactivation. The homozygous X /X mice produce uniform Cre activity in arterial SMCs.
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http://dx.doi.org/10.1002/dvg.23054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5753606PMC
September 2017