SAA LIPOPROTEIN FAMILY--FUNCTION & ROLE IN AMYLOIDOSIS

动脉粥样硬化病变的发病机制的研究一直由 几个假说：胆固醇假说一直是许多人的中心 多年来，并提供了丰硕的成果，但也发展了 这一过程涉及的不仅仅是脂肪沉积，而且 血管损伤可由各种因素引起，如氧化脂质， 病毒、氧自由基和脂类以外的物质可能会获得 通过血液进入血管壁。很明显， 各种有害因素引发了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 伤害必须在摧毁或移除有害物质之间保持平衡 实体和限制这一部分辩护的破坏性影响 系统。“反应型”淀粉样物质中的主肽 淀粉样蛋白来源于循环前体--血清淀粉样蛋白A 由肝脏分泌，与高密度脂蛋白相关，即AS 阿波萨斯。此外，它们是由各种细胞在当地产生的 包括参与动脉粥样硬化发展的那些类型的基因 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出现了几种功能 基因，包括脂溶毒素的封存，重定向 高密度脂蛋白的转运，对血小板聚集的干扰和 抑制白细胞功能。我们建议在活体内进行检测， 在体外实验中，apoSAAs的潜在调节活性 与局部对伤害性物质的反应有关，例如可能正在驾驶 动脉粥样硬化病变的发展。

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.