: The SCOR proposes an integrated set of basic and clinical studies aiming to define molecular mechanisms of atherogenesis at the level of the arterial wall. Effects on atherogenesis of arterial wall enzymes, lipoproteins and proteoglycans will be investigated in transgenic mouse models and in cell culture. A parallel set of investigations in humans will determine the relevance of mechanisms defined in mice and in cell culture to the pathophysiology of human atherosclerosis. Thus, the SCOR will define new mechanisms of atherogenesis and evaluate their significance in humans. Project 6 (Tall) will evaluate the mechanisms of atheroma foam cell regression that result from the interaction of HDL or its apolipoproteins with macrophage ABCA1. Project 1 (Tabas) will investigate the role of arterial wall sphingomyelinase in lipoprotein retention and aggregation, and macrophage foam cell formation. Project 7 (Williams) will evaluate the role of arterial wall proteoglycans in lipoprotein retention, and will study the mechanisms and significance of the recent finding that mice deficient in decorin proteoglycan have acclerated atherogenesis. Project 8 (Goldberg) will study the role of perlecan in atherogenesis, and will determine the role of this proteoglycan in preventing penetration of atherogenic lipoproteins into the arterial wall. The four cores will be A) Administrative; B) Clinical/Biostatistics; Q Gene Expression Profiling; and D) Pathology. The major theme of the SCOR is to investigate the interactions of plasma lipoproteins with proteoglycans, enzymes and cells of the arterial wall, and to define molecular mechanisms that promote or ameliorate atheroma foam cell formation. The studies are likely to reveal novel information about the role of specific arterial wall molecules in atherosclerosis in mice and humans, leading to improved diagnosis and treatment of this disease.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Specialized Center (P50)
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Special Emphasis Panel (ZHL1)
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Columbia University (N.Y.)
New York
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Chen, Han; Cade, Brian E; Gleason, Kevin J et al. (2018) Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men. Am J Respir Cell Mol Biol 58:391-401
Johnson, Dayna A; Hirsch, Jana A; Moore, Kari A et al. (2018) Associations Between the Built Environment and Objective Measures of Sleep: The Multi-Ethnic Study of Atherosclerosis. Am J Epidemiol 187:941-950
Johnson, Dayna A; Lane, Jacqueline; Wang, Rui et al. (2017) Greater Cognitive Deficits with Sleep-disordered Breathing among Individuals with Genetic Susceptibility to Alzheimer Disease. The Multi-Ethnic Study of Atherosclerosis. Ann Am Thorac Soc 14:1697-1705
Cade, Brian E; Chen, Han; Stilp, Adrienne M et al. (2016) Genetic Associations with Obstructive Sleep Apnea Traits in Hispanic/Latino Americans. Am J Respir Crit Care Med 194:886-897
Mayurasakorn, Korapat; Williams, Jill J; Ten, Vadim S et al. (2011) Docosahexaenoic acid: brain accretion and roles in neuroprotection after brain hypoxia and ischemia. Curr Opin Clin Nutr Metab Care 14:158-67
Devlin, Cecilia M; Leventhal, Andrew R; Kuriakose, George et al. (2008) Acid sphingomyelinase promotes lipoprotein retention within early atheromata and accelerates lesion progression. Arterioscler Thromb Vasc Biol 28:1723-30
Pan, Meihui; Maitin, Vatsala; Parathath, Sajesh et al. (2008) Presecretory oxidation, aggregation, and autophagic destruction of apoprotein-B: a pathway for late-stage quality control. Proc Natl Acad Sci U S A 105:5862-7
Williams, Kevin Jon; Feig, Jonathan E; Fisher, Edward A (2008) Rapid regression of atherosclerosis: insights from the clinical and experimental literature. Nat Clin Pract Cardiovasc Med 5:91-102
Tabas, Ira; Williams, Kevin Jon; Boren, Jan (2007) Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation 116:1832-44
Williams, Kevin Jon; Qiu, Gang; Usui, Hitomi Katoaka et al. (2007) Decorin deficiency enhances progressive nephropathy in diabetic mice. Am J Pathol 171:1441-50

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