SAA LIPOPROTEIN FAMILY--FUNCTION & ROLE IN AMYLOIDOSIS

SAA 脂蛋白家族--功能

• 批准号: 2219492
• 负责人: EARL P BENDITT
• 金额: $ 21.19万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2219492
• 关键词: amyloidosis; apolipoproteins; atherosclerosis; cell type; cellular pathology; cholesterol; disease /disorder classification; disease /disorder model; gene expression; high density lipoproteins; human tissue; immunochemistry; laboratory mouse; laboratory rabbit; lipid transport; neutrophil; platelet aggregation; tissue /cell culture; vascular smooth muscle

Studies of the pathogenesis of atherosclerotic lesions have been guided by several hypotheses: the cholesterol hypothesis has been central for many years and has provided fruitful However, there has developed appreciation of the fact that the process involves more than lipid deposition and that vascular injury may be caused by various agents such as oxidized lipids, viruses, oxygen free radicals and substances other than lipids may gain access to vessel walls via the blood. It has become evident that the various injurious agents invoke a large interconnected network of factors responsible for defending against a wide range of different insults. Moreover, for survival of an organism the responses evoked by various forms of injury must maintain a balance between destroying or removing a noxious entity and limiting the destructive effects of this part of the defense system. The main peptide in the amyloid substance of "reactive' type of amyloid derive from circulating precursors, serum amyloid A proteins secreted by the liver and associated with HDL lipoproteins, i.e. as apoSAAs. Furthermore they are produced locally by a variety of cells including those of the type involved in development of atherosclerotic plaque such as endothelial cells, vascular smooth muscle, and macrophages. Several functions seem to be emerging for products of this ancient family of genes including sequestration of lipid-soluble toxins, redirection of HDL cholesterol transport, interference with platelet aggregation and inhibition of leukocyte functions. We propose to examine, using in vivo and in vitro experiments, the potential modulator activities of the apoSAAs in relation to local reactions to injurious agents such as may be driving development of lesions of atherosclerosis.

动脉粥样硬化病变发病机制的研究一直以 几个假设：胆固醇假说一直是许多人的核心 多年来并取得了丰硕的成果，但人们已经形成了欣赏 事实上，这个过程不仅仅涉及脂质沉积，而且 血管损伤可能由多种因素引起，例如氧化脂质、 病毒、氧自由基和脂质以外的物质可能会增加 通过血液进入血管壁。 很明显， 各种有害因素会引发一个巨大的相互关联的因素网络 负责防御各种不同的侮辱。 此外，为了有机体的生存，各种形式引起的反应 伤害必须在破坏或消除有害物质之间保持平衡 实体并限制这部分防御的破坏性影响 系统。 “反应”型淀粉样物质中的主要肽 淀粉样蛋白源自循环前体、血清淀粉样蛋白 A 由肝脏分泌并与 HDL 脂蛋白相关，即 载脂蛋白SAA。 此外，它们是由多种细胞在本地产生的 包括那些参与动脉粥样硬化发展的类型 斑块如内皮细胞、血管平滑肌和巨噬细胞。 这个古老家族的产品似乎正在出现多种功能 基因的改变，包括脂溶性毒素的隔离、基因的重定向 HDL 胆固醇转运、干扰血小板聚集和 抑制白细胞功能。 我们建议使用体内检查 和体外实验，apoSAA 的潜在调节活性 与当地对伤害性因素（例如可能正在驾驶）的反应有关 动脉粥样硬化病变的发展。