کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2949411 1577317 2010 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
p19ARFDeficiency Reduces Macrophage and Vascular Smooth Muscle Cell Apoptosis and Aggravates Atherosclerosis
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
p19ARFDeficiency Reduces Macrophage and Vascular Smooth Muscle Cell Apoptosis and Aggravates Atherosclerosis
چکیده انگلیسی

ObjectivesThe goal of this study was to investigate the role in atherosclerosis of the tumor suppressor protein ARF (human p14ARF, mouse p19ARF) encoded by the CDKN2Agene.BackgroundAtherosclerosis is characterized by excessive proliferation and apoptosis, 2 cellular processes regulated by CDKN2A. Although recent genome-wide association studies have linked atherosclerotic diseases to a genomic region in human chromosome 9p21 near the CDKN2Alocus, the mechanisms underlying this gene–disease association remain undefined, and no causal link has been established between CDKN2Aand atherosclerosis.MethodsAtherosclerosis-prone apolipoprotein E (apoE)-null and doubly deficient apoE-p19ARFmice were fed an atherogenic diet and sacrificed to quantify atherosclerosis burden in whole-mounted aortas and in aortic cross-sections. Proliferation and apoptosis were investigated in atherosclerotic lesions and in primary cultures of macrophages and vascular smooth muscle cells obtained from both groups of mice.ResultsGenetic disruption of p19ARFin apoE-null mice augments aortic atherosclerosis without affecting body weight, plasma lipoproteins, or plaque's proliferative activity. Notably, p19ARFdeficiency significantly attenuates apoptosis both in atherosclerotic lesions and in cultured macrophages and vascular smooth muscle cells, 2 major cellular constituents of atheromatous plaques.ConclusionsOur findings establish a direct link between p19ARF, plaque apoptosis, and atherosclerosis, and suggest that human genetic variants associated to diminished CDKN2Aexpression may accelerate atherosclerosis by limiting plaque apoptosis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of the American College of Cardiology - Volume 55, Issue 20, 18 May 2010, Pages 2258–2268
نویسندگان
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