Arteriosclerosis, Thrombosis, & Vascular Biology最新文献

{"title":"NADPH Oxidase-2 and Atherothrombosis: Insight From Chronic Granulomatous Disease.","authors":"F. Violi, R. Carnevale, L. Loffredo, P. Pignatelli, J. Gallin","doi":"10.1161/ATVBAHA.116.308351","DOIUrl":"https://doi.org/10.1161/ATVBAHA.116.308351","url":null,"abstract":"The phagocytic cell enzyme NADPH oxidase-2 (Nox2) is critical for killing micro-organisms via production of reactive oxygen species and thus is a key element of the innate immune system. Nox2 is also detectable in endothelial cells and platelets where it has vasoconstrictive and aggregating properties, respectively. Patients with X-linked chronic granulomatous disease with hereditary Nox2 deficiency not only have impaired bacterial killing but, in association with loss of Nox2 function, also have enhanced carotid artery dilation, impaired platelet-related thrombosis, and reduced carotid atherosclerotic burden. Experimental studies corroborated these reports in chronic granulomatous disease by demonstrating (1) Nox2 is upregulated in atherosclerotic plaque, and this upregulation significantly correlates with oxidative stress and (2) pharmacological inhibition of Nox2 is associated with a delayed atherosclerotic progression in animal models. Furthermore, the role of Nox2 in platelet-associated thrombosis was substantiated by experiments showing impaired platelet activation in animals treated with a Nox2 inhibitor or impaired platelet aggregation along with reduced platelet-related thrombosis in the mouse knockout model of Nox2. Interestingly, in chronic granulomatous disease patients and in the mouse knockout model of Nox2, no defects of primary hemostasis were detected. This review analyses experimental and clinical data suggesting Nox2 is a potential target for counteracting the atherothrombotic process.","PeriodicalId":8404,"journal":{"name":"Arteriosclerosis, Thrombosis, & Vascular Biology","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80895112","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":"Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus.","authors":"K. Yahagi, F. Kolodgie, C. Lutter, Hiroyoshi Mori, Maria E. Romero, A. Finn, R. Virmani","doi":"10.1161/ATVBAHA.116.306256","DOIUrl":"https://doi.org/10.1161/ATVBAHA.116.306256","url":null,"abstract":"The continuing increase in the prevalence of diabetes mellitus in the general population is predicted to result in a higher incidence of cardiovascular disease. Although the mechanisms of diabetes mellitus-associated progression of atherosclerosis are not fully understood, at clinical and pathological levels, there is an appreciation of increased disease burden and higher levels of arterial calcification in these subjects. Plaques within the coronary arteries of patients with diabetes mellitus generally exhibit larger necrotic cores and significantly greater inflammation consisting mainly of macrophages and T lymphocytes relative to patients without diabetes mellitus. Moreover, there is a higher incidence of healed plaque ruptures and positive remodeling in hearts from subjects with type 1 diabetes mellitus and type 2 diabetes mellitus, suggesting a more active atherogenic process. Lesion calcification in the coronary, carotid, and other arterial beds is also more extensive. Although the role of coronary artery calcification in identifying cardiovascular disease and predicting its outcome is undeniable, our understanding of how key hormonal and physiological alterations associated with diabetes mellitus such as insulin resistance and hyperglycemia influence the process of vascular calcification continues to grow. Important drivers of atherosclerotic calcification in diabetes mellitus include oxidative stress, endothelial dysfunction, alterations in mineral metabolism, increased inflammatory cytokine production, and release of osteoprogenitor cells from the marrow into the circulation. Our review will focus on the pathophysiology of type 1 diabetes mellitus- and type 2 diabetes mellitus-associated vascular disease with particular focus on coronary and carotid atherosclerotic calcification.","PeriodicalId":8404,"journal":{"name":"Arteriosclerosis, Thrombosis, & Vascular Biology","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85147505","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":"DNA Methylation and High-Density Lipoprotein Functionality-Brief Report: The REGICOR Study (Registre Gironi del Cor).","authors":"S. Sayols-Baixeras, Á. Hernáez, I. Subirana, C. Lluís-Ganella, D. Muñoz, M. Fitó, J. Marrugat, R. Elosúa","doi":"10.1161/ATVBAHA.116.308831","DOIUrl":"https://doi.org/10.1161/ATVBAHA.116.308831","url":null,"abstract":"OBJECTIVE\u0000The function of high-density lipoproteins (HDLs) may better reflect their atheroprotective role, compared with HDL-cholesterol levels. The association between DNA methylation and HDL function has not yet been established.\u0000\u0000\u0000APPROACH AND RESULTS\u0000We designed an epigenome-wide association study including 645 individuals from the REGICOR study (Registre Gironi del Cor). We determined DNA methylation from peripheral blood cells using the HumanMethylation450 array. We analyzed HDL functionality by determining HDL cholesterol efflux capacity and HDL inflammatory index. We discovered 3 methylation sites located in HOXA3, PEX5, and PER3 related to cholesterol efflux capacity and 1 located in GABRR1 related to HDL inflammatory index. Using a candidate gene approach, we also found 2 methylation sites located in CMIP related to cholesterol efflux capacity.\u0000\u0000\u0000CONCLUSIONS\u0000We identified 6 potential loci associated with HDL functionality in HOXA3, PEX5, PER3, CMIP, and GABRR1. Additional studies are warranted to validate these findings in other populations.","PeriodicalId":8404,"journal":{"name":"Arteriosclerosis, Thrombosis, & Vascular Biology","volume":"94 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75737663","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":"ATVB Named Lecture Review-Insight Into Author.","authors":"L. Wilkins","doi":"10.1161/ATV.0000000000000041","DOIUrl":"https://doi.org/10.1161/ATV.0000000000000041","url":null,"abstract":"ATVB Named Lecture Reviews—2013 Jeffrey M. Hoeg ATVB Award for Basic Science and Clinical Research Insight Into the Author: Susan S. Smyth, MD, PhD, University of Kentucky According to my mother, I was always very curious as a child, bringing creatures such as snakes and frogs into the house and putting them in the bathtub to watch. In high school, I had a fantastic AP biology course that first opened my eyes to science. I entered college with the intent of being a biology major, and my enthusiasm for science grew at Mount Holyoke. Ultimately, I decided that pursuing dual MD and PhD training would provide me with the broadest possible education. During my clinical training, abciximab received approval as adjunctive therapy for angioplasty. Having used the parent molecule monoclonal antibody 7E3 in experiments as a graduate student, it was a career-changing experience to administer abciximab to patients. That is when I realized that a career in cardiovascular medicine was my future. I have been incredibly fortunate to have had the …","PeriodicalId":8404,"journal":{"name":"Arteriosclerosis, Thrombosis, & Vascular Biology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88219035","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":"ATVB Named Lecture Review-Insight Into Author.","authors":"","doi":"10.1161/ATV.0000000000000044","DOIUrl":"https://doi.org/10.1161/ATV.0000000000000044","url":null,"abstract":"","PeriodicalId":8404,"journal":{"name":"Arteriosclerosis, Thrombosis, & Vascular Biology","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78469785","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":"ATVB Named Lecture Review-Insight Into Author.","authors":"","doi":"10.1161/ATV.0000000000000042","DOIUrl":"https://doi.org/10.1161/ATV.0000000000000042","url":null,"abstract":"","PeriodicalId":8404,"journal":{"name":"Arteriosclerosis, Thrombosis, & Vascular Biology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78917566","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":"The Microvasculature: The Next Battlefield Where Transforming Growth Factor-β and Endoglin Draw Their Double-Edged Swords?","authors":"G. Pasterkamp, M. Goumans","doi":"10.1161/ATVBAHA.116.308610","DOIUrl":"https://doi.org/10.1161/ATVBAHA.116.308610","url":null,"abstract":"Regenerative tissue repair after injury is a delicate balance between pivotal biological processes, such as cell growth and differentiation, angiogenesis, and extracellular matrix remodeling. The notice that damage repair comes with enhanced angiogenic and profibrotic responses has inspired the scientific community with the idea that molecules involved in collagen turnover and proteolysis may act as biomarkers to predict remission or activation of chronic inflammatory diseases in which fibrosis is one of the major underlying key players. See accompanying article on page 49 Transforming growth factor-β (TGF-β) is a critical growth factor in tissue repair. TGF-β belongs to a large family of growth factors to which also the bone morphogenetic proteins (BMPs) belong.1 TGF-β has many functions such as inhibition of epithelial and endothelial cell growth, stimulation of mesenchymal cell growth, and diminishing the inflammatory response, but its most important role in tissue repair is to promote extracellular matrix turnover. Although TGF-β1 has proarteriogenic and angiogenic effects, depending on the context and concentration, TGF-β can also be antiangiogenic, inhibiting the growth of endothelial cells.2 Therefore, it plays a pivotal role during vascular homeostasis and maintenance. TGF-β1 seems a double-edged sword in vascular occlusive diseases. On one hand, it enhances smooth muscle cell proliferation and stimulates extracellular matrix production, 2 key components of restenosis and vessel remodeling. On the other hand, an increase in smooth muscle cell content and a thick fibrotic cap are also features of stable atherosclerotic lesions that are less prone to rupture. Endoglin is an accessory TGF-β receptor and a modulator of TGF-β signaling.3 Endoglin plays an important regulatory role in balancing the proangiogenic and antiangiogenic and fibrotic response of TGF-β. Endoglin exerts its function by interacting with the TGF-β type II receptor and the type 1 receptors ALK1 (activin receptor-like kinase) and ALK5 and …","PeriodicalId":8404,"journal":{"name":"Arteriosclerosis, Thrombosis, & Vascular Biology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86572891","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":"Monocyte Conversion During Inflammation and Injury.","authors":"Rachel M. Kratofil, P. Kubes, J. Deniset","doi":"10.1161/ATVBAHA.116.308198","DOIUrl":"https://doi.org/10.1161/ATVBAHA.116.308198","url":null,"abstract":"Monocytes are circulating leukocytes important in both innate and adaptive immunity, primarily functioning in immune defense, inflammation, and tissue remodeling. There are 2 subsets of monocytes in mice (3 subsets in humans) that are mobilized from the bone marrow and recruited to sites of inflammation, where they carry out their respective functions in promoting inflammation or facilitating tissue repair. Our understanding of the fate of these monocyte subsets at the site of inflammation is constantly evolving. This brief review highlights the plasticity of monocyte subsets and their conversion during inflammation and injury.","PeriodicalId":8404,"journal":{"name":"Arteriosclerosis, Thrombosis, & Vascular Biology","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82721298","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":"Sphingolipids Contribute to Human Atherosclerotic Plaque Inflammation.","authors":"A. Edsfeldt, P. Dunér, M. Ståhlman, I. Mollet, G. Asciutto, H. Grufman, M. Nitulescu, A. Persson, R. Fisher, O. Melander, M. Orho-Melander, J. Borén, J. Nilsson, I. Gonçalves","doi":"10.1161/ATVBAHA.116.305675","DOIUrl":"https://doi.org/10.1161/ATVBAHA.116.305675","url":null,"abstract":"OBJECTIVE\u0000Lipids are central to the development of atherosclerotic plaques. Specifically, which lipids are culprits remains controversial, and promising targets have failed in clinical studies. Sphingolipids are bioactive lipids present in atherosclerotic plaques, and they have been suggested to have both proatherogenic and antiatherogenic. However, the biological effects of these lipids remain unknown in the human atherosclerotic plaque. The aim of this study was to assess plaque levels of sphingolipids and investigate their potential association with and contribution to plaque vulnerability.\u0000\u0000\u0000APPROACH AND RESULTS\u0000Glucosylceramide, lactosylceramide, ceramide, dihydroceramide, sphingomyelin, and sphingosine-1-phosphate were analyzed in homogenates from 200 human carotid plaques using mass spectrometry. Inflammatory activity was determined by analyzing plaque levels of cytokines and plaque histology. Caspase-3 was analyzed by ELISA technique. Expression of regulatory enzymes was analyzed with RNA sequencing. Human coronary artery smooth muscle cells were used to analyze the potential role of the 6 sphingolipids as inducers of plaque inflammation and cellular apoptosis in vitro. All sphingolipids were increased in plaques associated with symptoms and correlated with inflammatory cytokines. All sphingolipids, except sphingosine-1-phosphate, also correlated with histological markers of plaque instability. Lactosylceramide, ceramide, sphingomyelin, and sphingosine-1-phosphate correlated with caspase-3 activity. In vitro experiments revealed that glucosylceramide, lactosylceramide, and ceramide induced cellular apoptosis. All analyzed sphingolipids induced an inflammatory response in human coronary artery smooth muscle cells.\u0000\u0000\u0000CONCLUSIONS\u0000This study shows for the first time that sphingolipids and particularly glucosylceramide are associated with and are possible inducers of plaque inflammation and instability, pointing to sphingolipid metabolic pathways as possible novel therapeutic targets.","PeriodicalId":8404,"journal":{"name":"Arteriosclerosis, Thrombosis, & Vascular Biology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89771645","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":"Recipients of the 2015 Early Career Investigator Awards.","authors":"A. Daugherty","doi":"10.1161/ATVBAHA.116.307358","DOIUrl":"https://doi.org/10.1161/ATVBAHA.116.307358","url":null,"abstract":"This is the 11th year of competition for ATVB Early Career Investigator Awards. The Awards recognize papers published in ATVB in 2015 that were submitted by new investigators and judged to be the most outstanding in the Atherosclerosis/Lipoprotein, Thrombosis, and Vascular Biology sections of the journal. The 3 awards are named for Dr Daniel Steinberg, who devised a method to determine the site of degradation of the proteins and lipids …","PeriodicalId":8404,"journal":{"name":"Arteriosclerosis, Thrombosis, & Vascular Biology","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77691932","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}