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Role of Serum Amyloid A in Atheroscierosis

血清淀粉样蛋白 A 在动脉粥样硬化中的作用

基本信息

批准号：
7923958
负责人：
LISA R TANNOCK
金额：
$ 39.27万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7923958
关键词：
Accounting Acute Adenoviruses Affinity Animal Model Animals Apolipoproteins Arterial Fatty Streak Atherosclerosis Attenuated Binding Blood Vessels C-reactive protein Cardiac Cardiovascular Diseases Cause of Death Clinical Data Developed Countries Development Diabetes Mellitus Event Foam Cells Goals Grant High Density Lipoproteins Human Immunodeficient Mouse In Vitro Individual Injection of therapeutic agent Intervention Knockout Mice Lipoprotein Binding Lipoproteins Low-Density Lipoproteins Mediating Mediator of activation protein Medical Metabolic syndrome Methodology Modeling Mus Obese Mice Obesity Phase Plasma Play Principal Investigator Property Protein Isoforms Proteoglycan Public Health Recombinants Risk Risk Factors Role Serum amyloid A protein Testing Very low density lipoprotein base biglycan cardiovascular disorder risk in vivo inflammatory marker macrophage programs response

项目摘要

Cardiovascular disease is the leading cause of death in developed countries. Individuals with obesity, metabolic syndrome, and/or diabetes are at markedly increased risk of atherosclerotic cardiovascular disease although the underlying mechanisms are not fully understood. The retention of atherogenic lipoproteins within the subendothelial space of the arterial wall by their interactions with vascular proteoglycans is thought to be a key step in the initiation of atherosclerosis, as outlined in the “Response to Retention Hypothesis”. Obesity, the metabolic syndrome and diabetes all are associated with increased levels of inflammatory markers including serum amyloid A (SAA), and SAA levels are predictive of cardiovascular disease in humans and in animal models. The central hypothesis of this grant is that SAA is pro-atherogenic. This hypothesis is based on several key observations: (a) SAA is present within atherosclerotic lesions in close association to apolipoproteins and proteoglycans; (b) We recently demonstrated that SAA alters vascular proteoglycan synthesis in a pro-atherogenic manner; (c) SAA is an apolipoprotein that is capable of binding to proteoglycans, and thus may facilitate the retention of lipoproteins on which it is carried; (d) In preliminary studies we demonstrate accelerated atherosclerosis in mice in which SAA is over-expressed. Thus, SAA may in fact be a mediator of atherosclerosis by leading to increased retention of atherogenic lipoproteins by vascular proteoglycans. We will test this hypothesis by evaluating the effect of SAA over-expression on vascular proteoglycan synthesis, lipoprotein retention and atherosclerosis development using in vivo methodology. Given the increased SAA levels observed in obesity, metabolic syndrome and diabetes, we propose that SAA may be a mechanism contributing to the increased cardiovascular disease in these conditions. Program Director/Principal Investigator (Last, First, Middle): Tannock, Lisa R.

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