Arteriosclerosis, Thrombosis, & Vascular Biology最新文献

{"title":"Smooth Muscle Cells in Vascular Remodeling.","authors":"Ning Shi, Xiaohan Mei, Shi-You Chen","doi":"10.1161/ATVBAHA.119.312581","DOIUrl":"https://doi.org/10.1161/ATVBAHA.119.312581","url":null,"abstract":"As the primary causes of myocardial infarction, stroke, atherosclerosis, in-stent restenosis, and aneurysm, aortic diseases pose a serious threat to human health. Arterial remodeling is considered to be an important mechanism underlying the development of arterial diseases. Arterial remodeling refers to structural and functional alterations in arterial wall in response to vascular injury or aging. Vascular smooth muscle cells (SMCs), a major component of the arterial wall, exhibit remarkable phenotypic plasticity and can dedifferentiate from a contractile state to a synthetic state, along with increased proliferation and migration abilities.1 Phenotypically modified SMCs play a major role in arterial remodeling.1 Recent publications in ATVB have delineated new pathways or factors that are involved in SMC phenotypic modulation and arterial remodeling. These studies have provided valuable insights for better understanding of regulatory mechanisms responsible for vascular remodeling. This article highlights studies on this topic that have published in ATVB recently.","PeriodicalId":8404,"journal":{"name":"Arteriosclerosis, Thrombosis, & Vascular Biology","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91153129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myocardin and Kv1 Channels: A Paradigm Shift in Treating Vascular Smooth Muscle Cell-Related Proliferative Disease?","authors":"David X. Zhang, D. Gutterman","doi":"10.1161/ATVBAHA.119.313531","DOIUrl":"https://doi.org/10.1161/ATVBAHA.119.313531","url":null,"abstract":"","PeriodicalId":8404,"journal":{"name":"Arteriosclerosis, Thrombosis, & Vascular Biology","volume":"145 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86215390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ten-Year Clinical Outcomes of Late-Acquired Stent Malapposition After Coronary Stent Implantation.","authors":"Seung‐Yul Lee, Jung‐Min Ahn, G. Mintz, Sung‐Jin Hong, C. Ahn, Duk‐Woo Park, Jung‐Sun Kim, Byeong‐Keuk Kim, Y. Ko, D. Choi, Y. Jang, Seung‐Jung Park, M. Hong","doi":"10.1161/ATVBAHA.119.313602","DOIUrl":"https://doi.org/10.1161/ATVBAHA.119.313602","url":null,"abstract":"OBJECTIVE\u0000The goal of this study was to determine the impact of late-acquired stent malapposition (LASM) on long-term clinical outcomes in patients treated with coronary stent implantation. Approach and Results: We investigated major adverse cardiac event during 10 years after 6-month intravascular ultrasound examination using our previous studies database. A total of 732 patients treated with bare-metal stent (54 LASM versus 678 non-LASM) and 529 patients treated with first-generation drug-eluting stent (82 LASM versus 447 non-LASM), who did not have clinical event or censoring at the time of follow-up intravascular ultrasound, were included for the present analysis. major adverse cardiac event was defined as the composite of cardiac death, target vessel-related myocardial infarction, target lesion revascularization and stent thrombosis. Multivariable adjustment and inverse probability weight were performed to consider baseline differences. After multivariable adjustment, LASM was related to a greater risk of major adverse cardiac event (hazard ratio, 1.666 [95% CI, 1.041-2.665]; P=0.0333) and very-late stent thrombosis (hazard ratio, 3.529 [95% CI, 1.153-10.798]; P=0.0271) than non-LASM in patients treated with first-generation drug-eluting stent, but not in those treated with bare-metal stent. Results were consistent after inverse probability weight. Among patients with LASM of first-generation drug-eluting stent, no late stent thrombosis occurred in patients who continued to receive dual antiplatelet therapy.\u0000\u0000\u0000CONCLUSIONS\u0000The relationship between LASM and major adverse cardiac event might depend on the type of implanted stents during the long-term follow-up, highlighting the clinical significance of polymers and drugs in drug-eluting stent system.","PeriodicalId":8404,"journal":{"name":"Arteriosclerosis, Thrombosis, & Vascular Biology","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87518046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter by Agbani et al Regarding Article, \"Clot Contraction Drives the Translocation of Procoagulant Platelets to Thrombus Surface\".","authors":"E. Agbani, I. Hers, A. Poole","doi":"10.1161/ATVBAHA.119.313468","DOIUrl":"https://doi.org/10.1161/ATVBAHA.119.313468","url":null,"abstract":"","PeriodicalId":8404,"journal":{"name":"Arteriosclerosis, Thrombosis, & Vascular Biology","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90038503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex Differences in Genomic Drivers of Adipose Distribution and Related Cardiometabolic Disorders: Opportunities for Precision Medicine.","authors":"H. Lumish, M. O'Reilly, M. Reilly","doi":"10.1161/ATVBAHA.119.313154","DOIUrl":"https://doi.org/10.1161/ATVBAHA.119.313154","url":null,"abstract":"This review focuses on the human genetics, epidemiology, and molecular pathophysiology of sex differences in central obesity, adipose distribution, and related cardiometabolic disorders. Distribution of fat is important for cardiometabolic health, with peripheral fat depots having a protective effect and central visceral fat depots conferring a detrimental effect on health. There are important sex differences in fat distribution that are masked when studying body mass index as a measure of obesity. From epidemiological, murine, and in vitro studies, several mechanisms have been proposed to explain the sex differences in adipose distribution, including sex hormonal effects, cell-intrinsic properties, and the microenvironment in fat depots. More recently, human genetics have revealed hundreds of loci for central obesity providing disruptive opportunities for mechanistic discoveries and clinical translation. A striking feature is that over one-third of these loci have reproducible but poorly understood sexual dimorphic associations with central obesity, most having stronger effects in women. Understanding the genetic and molecular mechanisms of adipose distribution and its sexual dimorphism in humans provides a unique opportunity to advance mechanism-based, sex and gender aware, precision medicine for early identification of at-risk individuals, as well as novel therapeutic strategies for central obesity and cardiometabolic disorders.","PeriodicalId":8404,"journal":{"name":"Arteriosclerosis, Thrombosis, & Vascular Biology","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84633949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S-Nitrosylation of Plastin-3 Exacerbates Thoracic Aortic Dissection Formation via Endothelial Barrier Dysfunction.","authors":"Lihong Pan, Zhe Lin, Xin Tang, Jiaxin Tian, Qiao Zheng, Jin Jing, Liping Xie, Hongshan Chen, Qiulun Lu, Hong Wang, Qingguo Li, Yi Han, Yong Ji","doi":"10.1161/ATVBAHA.119.313440","DOIUrl":"https://doi.org/10.1161/ATVBAHA.119.313440","url":null,"abstract":"OBJECTIVE\u0000Thoracic aortic dissection (TAD) is a fatal disease that leads to aortic rupture and sudden death. However, little is known about the effect and molecular mechanism of S-nitrosylation (SNO) modifications in TAD formation. Approach and Results: SNO levels were higher in aortic tissues from TAD patients than in those from healthy controls, and PLS3 (plastin-3) SNO was identified by liquid chromatography-tandem mass spectrometry analysis. Furthermore, tail vein administration of endothelial-specific adeno-associated viruses of mutant PLS3-C566A (denitrosylated form) suppressed the development of TAD in mice, but the wild-type PLS3 (S-nitrosylated form) virus did not. Mechanistically, Ang II (angiotensin II)-induced PLS3 SNO enhanced the association of PLS3 with both plectin and cofilin via an iNOS (inducible nitric oxide synthase)-dependent pathway in endothelial cells. The formation of PLS3/plectin/cofilin complex promoted cell migration and tube formation but weakened adherens junction formation in Ang II-treated endothelial cells. Interestingly, denitrosylated form of PLS3 partially mitigated Ang II-induced PLS3/plectin/cofilin complex formation and cell junction disruption. Additionally, the inhibition of iNOS attenuated PLS3 SNO and the association of PLS3 with plectin and cofilin, thereby modulating endothelial barrier function.\u0000\u0000\u0000CONCLUSIONS\u0000Our data indicate that protein SNO modification in endothelial cells modulates the progression of aortic aneurysm and dissection. The iNOS-mediated SNO of PLS3 at the Cys566 site promoted its interaction with cofilin and plectin, thus contributing to endothelial barrier disruption and pathological angiogenesis in TAD.","PeriodicalId":8404,"journal":{"name":"Arteriosclerosis, Thrombosis, & Vascular Biology","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87514136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Adenosine Monophosphate-Activated Protein Kinase-α2 Deficiency Promotes Vascular Smooth Muscle Cell Migration via S-Phase Kinase-Associated Protein 2 Upregulation and E-Cadherin Downregulation.","authors":"","doi":"10.1161/atv.0000000000000088","DOIUrl":"https://doi.org/10.1161/atv.0000000000000088","url":null,"abstract":"","PeriodicalId":8404,"journal":{"name":"Arteriosclerosis, Thrombosis, & Vascular Biology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81600843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"C-X-C Ligand 16 Is an Independent Predictor of Cardiovascular Death and Morbidity in Acute Coronary Syndromes.","authors":"Thomas Andersen, Thor Ueland, Tatevik Ghukasyan Lakic, Axel Åkerblom, Maria Bertilsson, Pål Aukrust, Annika E Michelsen, Stefan K James, Richard C Becker, Robert F Storey, Lars Wallentin, Agneta Siegbahn, Frederic Kontny","doi":"10.1161/ATVBAHA.119.312633","DOIUrl":"10.1161/ATVBAHA.119.312633","url":null,"abstract":"<p><strong>Objective: </strong>The chemokine CXCL16 (C-X-C motif ligand 16) is a scavenger receptor for OxLDL (oxidized low-density lipoproteins) and involved in inflammation at sites of atherosclerosis. This study aimed to investigate the association of CXCL16 with clinical outcome in patients with acute coronary syndrome. Approach and Results: Serial measurements of CXCL16 were performed in a subgroup of 5142 patients randomized in the PLATO trial (Platelet Inhibition and Patient Outcome). Associations between CXCL16 and a composite of cardiovascular death, spontaneous myocardial infarction or stroke, and the individual components were assessed by multivariable Cox regression analyses. The hazard ratio per 50% increase in admission levels of CXCL16 analyzed as continuous variable was 1.64 (95% CI, 1.44-1.88), <i>P</i><0.0001. This association remained statistically significant after adjustment for randomized treatment, clinical variables, CRP (C-reactive protein), leukocytes, cystatin C, NT-proBNP (N-terminal pro-brain natriuretic peptide), troponin T, GDF-15 (growth differentiation factor 15), and other biomarkers; hazard ratio 1.23 (1.05-1.45), <i>P</i>=0.0126. The admission level of CXCL16 was independently associated with cardiovascular death (1.50 [1.17-1.92], <i>P</i>=0.0014) but not with ischemic events alone, in fully adjusted analyses. No statistically independent association was found between CXCL16 measured at 1 month, or change in CXCL16 from admission to 1 month, and clinical outcomes.</p><p><strong>Conclusions: </strong>In patients with acute coronary syndrome, admission level of CXCL16 is independently related to adverse clinical outcomes, mainly driven by an association to cardiovascular death. Thus, CXCL16 measurement may enhance risk stratification in patients with this condition.</p><p><strong>Clinical trial registration: </strong>URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.</p>","PeriodicalId":8404,"journal":{"name":"Arteriosclerosis, Thrombosis, & Vascular Biology","volume":"105 1","pages":"2402-2410"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75214984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Characterization of LIPA (Lysosomal Acid Lipase) Variants Associated With Coronary Artery Disease.","authors":"T. Evans, Xiangyu Zhang, Reece E Clark, A. Alisio, Eric Song, Hanrui Zhang, M. Reilly, N. Stitziel, B. Razani","doi":"10.1161/ATVBAHA.119.313443","DOIUrl":"https://doi.org/10.1161/ATVBAHA.119.313443","url":null,"abstract":"OBJECTIVE\u0000LIPA (lysosomal acid lipase) mediates cholesteryl ester hydrolysis, and patients with rare loss-of-function mutations develop hypercholesterolemia and severe disease. Genome-wide association studies of coronary artery disease have identified several tightly linked, common intronic risk variants in LIPA which unexpectedly associate with increased mRNA expression. However, an exonic variant (rs1051338 resulting in T16P) in linkage with intronic variants lies in the signal peptide region and putatively disrupts trafficking. We sought to functionally investigate the net impact of this locus on LIPA and whether rs1051338 could disrupt LIPA processing and function to explain coronary artery disease risk. Approach and Results: In monocytes isolated from a large cohort of healthy individuals, we demonstrate both exonic and intronic risk variants are associated with increased LIPA enzyme activity coincident with the increased transcript levels. To functionally isolate the impact of rs1051338, we studied several in vitro overexpression systems and consistently observed no differences in LIPA expression, processing, activity, or secretion. Further, we characterized a second common exonic coding variant (rs1051339), which is predicted to alter LIPA signal peptide cleavage similarly to rs1051338, yet is not linked to intronic variants. rs1051339 also does not impact LIPA function in vitro and confers no coronary artery disease risk.\u0000\u0000\u0000CONCLUSIONS\u0000Our findings show that common LIPA exonic variants in the signal peptide are of minimal functional significance and suggest coronary artery disease risk is instead associated with increased LIPA function linked to intronic variants. Understanding the mechanisms and cell-specific contexts of LIPA function in the plaque is necessary to understand its association with cardiovascular risk.","PeriodicalId":8404,"journal":{"name":"Arteriosclerosis, Thrombosis, & Vascular Biology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82286032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tapping Into the Strengths of Diversity Among Atherosclerotic Pigs.","authors":"J. Bentzon","doi":"10.1161/ATVBAHA.119.313404","DOIUrl":"https://doi.org/10.1161/ATVBAHA.119.313404","url":null,"abstract":"Arterioscler Thromb Vasc Biol. 2019;39:2203–2204. DOI: 10.1161/ATVBAHA.119.313404 November 2019 2203 Correspondence to: Jacob F. Bentzon, MD, PhD, Centro Nacional de Investigaciones Cardiovasculares (CNIC) Carlos III (FSP), C/Melchor Fernández Almagro 3, 28029 Madrid, Spain. Email jfbentzon@cnic.es For Sources of Funding and Disclosures, see page 2204. © 2019 American Heart Association, Inc. EDITORIAL","PeriodicalId":8404,"journal":{"name":"Arteriosclerosis, Thrombosis, & Vascular Biology","volume":"806 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85459001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}