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

• 批准号: 7692735
• 负责人: LISA R TANNOCK
• 金额: $ 40.65万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7692735
• 关键词: Adenoviruses; Affect; Animal Model; Animals; Apolipoprotein E; Apolipoproteins; Arterial Fatty Streak; Atherosclerosis; Backcrossings; Beer; Binding; Blood Vessels; Cardiovascular Diseases; Cause of Death; Characteristics; Cholesterol; Data; Developed Countries; Developing Countries; Development; Diabetes Mellitus; Diet; Funding; Goals; Grant; Human; Immunocompetent; Immunodeficient Mouse; Individual; Injection of therapeutic agent; Knockout Mice; Laboratories; Lead; Length; Lipids; Lipoproteins; Measures; Mediating; Mediator of activation protein; Medical; Metabolic syndrome; Methodology; Modeling; Mus; Obesity; Parents; Personal Communication; Plasma; Principal Investigator; Property; Proteoglycan; Risk; Role; Saline; Serum amyloid A protein; Testing; Time; TimeLine; Transgenic Mice; Up-Regulation; Viral; Virus; adenoviral-mediated; base; biglycan; feeding; in vivo; inflammatory marker; parent grant; programs; research study; response; trend; Adenoviruses; Affect; Animal Model; Animals; Apolipoprotein E; Apolipoproteins; Arterial Fatty Streak; Atherosclerosis; Backcrossings; Beer; Binding; Blood Vessels; Cardiovascular Diseases; Cause of Death; Characteristics; Cholesterol; Data; Developed Countries; Developing Countries; Development; Diabetes Mellitus; Diet; Funding; Goals; Grant; Human; Immunocompetent; Immunodeficient Mouse; Individual; Injection of therapeutic agent; Knockout Mice; Laboratories; Lead; Length; Lipids; Lipoproteins; Measures; Mediating; Mediator of activation protein; Medical; Metabolic syndrome; Methodology; Modeling; Mus; Obesity; Parents; Personal Communication; Plasma; Principal Investigator; Property; Proteoglycan; Risk; Role; Saline; Serum amyloid A protein; Testing; Time; TimeLine; Transgenic Mice; Up-Regulation; Viral; Virus; adenoviral-mediated; base; biglycan; feeding; in vivo; inflammatory marker; parent grant; programs; research study; response; trend

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.

心血管疾病是死亡的主要原因 发达国家。患有肥胖，代谢综合征和/或糖尿病的人明显 动脉粥样硬化心血管疾病的风险增加了 理解齿。通过 他们与血管蛋白聚糖的相互作用被认为是动脉粥样硬化的主动性的关键步骤， 如“对保留假设的响应”中概述。肥胖，代谢综合征和糖尿病 与包括血清淀粉样蛋白A（SAA）和SAA在内的炎症标记水平增加有关 水平可以预测人类和动物模型中的心血管疾病。中心假设 这笔赠款是SAA具有亲动脉粥样硬化。该假设基于几个关键观察：（a）SAA是 存在于动脉粥样硬化病变中，与载脂蛋白和蛋白聚糖密切相关； （b）我们 最近证明，SAA以亲动遗传学的方式改变了血管蛋白聚糖的合成。 （C） SAA是一种能够与蛋白聚糖结合的载脂蛋白，因此可能有助于保留 携带脂蛋白； （d）在初步研究中，我们证明了动脉粥样硬化的加速 SAA过表达的小鼠。这就是SAA实际上可能是通过导致动脉粥样硬化的调解人 通过血管蛋白聚糖增加了动脉粥样硬化脂蛋白的保留。我们将通过 评估SAA过表达对血管蛋白聚糖合成，脂蛋白保留和 使用体内方法论开发动脉粥样硬化。鉴于在 肥胖，代谢综合征和糖尿病，我们建议SAA可能是有助于 在这些条件下，心血管疾病增加。 计划主任/首席研究员（最后，第一，中间）：坦诺克，丽莎·R。