SAA LIPOPROTEIN FAMILY--FUNCTION & ROLE IN AMYLOIDOSIS

淀粉样变性包括一组特征为以下的病症： 蛋白质纤维的细胞外积累。 的分布 这些纤维位于受影响器官的内皮下位置， 血管可能导致重要器官的最终损伤 功能协调发展的 山茱萸主要多肽成分的分析 淀粉样蛋白沉积揭示了从正常的 血浆成分 血清淀粉样蛋白A（apoSAA）是血浆高密度脂蛋白（HDL）的一个独特家族 脱辅基蛋白是淀粉样蛋白A原纤维蛋白的前体， AA型淀粉样变性。 没有什么是已知的功能（S） 关于他们的作用，人们知之甚少。 淀粉样变性的发展。 该项目的主要目标是：1） 为了阐明SAA脱辅基蛋白家族的功能，2） 探讨AA品种的发病机制 淀粉样变性和3）问是否，如果是，在什么方面， AA型淀粉样蛋白生成的基本原理是相关的 其他类型的淀粉样变性。 小鼠模型系统将 用来继续我们的调查 我们会找出 负责合成SAA 1、SAA 2和SAA 3 mRNA的类型。 我们将鉴定SAA 3脱辅基蛋白并检查组织 三种SAA脱辅基蛋白的相互作用和命运。 成纤维细胞，巨噬细胞，内皮细胞，平滑肌细胞， 检查肾上腺是否存在apoSAA HDL特异性受体。 如果apoSAA HDL受体 我们将确定它是否与HDL不同 受体，无论它是在响应损伤或 炎症条件，什么细胞类型拥有它，以及是否 其水平在淀粉样组织中升高。 的可能性 将测试SAA改变HDL的胆固醇转运活性。 apoSAA-HDL与细胞或基质相互作用的作用 成分将探讨AA型的发病机制 淀粉样变性

Amyloidosis comprises a group of disorders characterized by the extracellular accumulation of protein fibrils. The distribution of such fibrils in subendothelial locations of affected organs and vessels can lead to the eventual impairment of vital organ functions. Analysis of the major polypeptide constituents of amyloid deposits reveals distinct classes derived from normal plasma constituents. Serum amyloid A (apoSAA) is a unique family of plasma HDL apoproteins that are precursors of the amyloid A fibril protein of AA type amyloidosis. Nothing is known about the function(s) of the apoSAA's and little is known concerning their role in the development of amyloidosis. The major aims of this project are 1) to elucidate the function(s) of the SAA apoprotein family, 2) to investigate the mechanisms of the pathogenesis of the AA variety of amyloidosis and 3) to ask whether and, if so, in what ways the principles underlying amyloidogenesis of the AA type are relevant to other types of amyloidosis. The mouse model system will be used to continue our investigations. We will identify the cell types responsible for synthesis of SAA1, SAA2 and SAA3 mRNA. We will identify the SAA3 apoprotein and examine the tissue interactions and fate of the three SAA apoproteins. Fibroblasts, macrophages, endothelial cells, smooth muscle cells, and adrenal gland will be examined for the presence of apoSAA HDL-specific receptors. If the apoSAA HDL receptor is identified, we will ascertain whether it is distinct from the HDL receptor, whether it is regulated in response to injury or inflammatory conditions, what cell types possess it, and whether its levels are elevated in amyloidotic tissues. The possibility that SAA alters cholesterol transport activities of HDL will be tested. The role of apoSAA-HDL interaction with cells or matrix components will be explored in regard to pathogenesis of AA type amyloidosis.