SAA LIPOPROTEIN FAMILY--FUNCTION & ROLE IN AMYLOIDOSIS

淀粉样变性包括一组疾病，其特征是 细胞外蛋白质纤维的堆积。分布情况： 这些纤维位于受影响器官的内皮下位置和 血管最终会导致重要器官的损害。 功能。红豆杉的主要多肽成分分析 淀粉样蛋白沉积显示出来自正常的不同类别 血浆成分。 血清淀粉样蛋白A(ApoSAA)是血浆高密度脂蛋白的一个独特家族 作为淀粉样蛋白A纤维蛋白前体的载脂蛋白 AA型淀粉样变性。关于S的作用，我们一无所知。 ApoSAA的作用和对它们在 淀粉样变性的发展。本项目的主要目标是1) 为了阐明SAA载脂蛋白家族的功能(S)，2) 探讨AA变种的致病机制 和3)询问是否以及如果是，以什么方式 AA型淀粉样变的潜在原理是相关的 其他类型的淀粉样变性。鼠标模型系统将是 用于继续我们的调查。我们会辨认出这个细胞 负责合成SAA1、SAA2和SAA3mRNA的类型。 我们将鉴定SAA3载脂蛋白并检查组织 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、 肾上腺将检查apoSAA的存在 高密度脂蛋白特异性受体。如果apoSAA高密度脂蛋白受体是 ，我们将确定它是否与高密度脂蛋白有所不同 受体，无论它是在损伤反应中被调节还是在 炎症状态，什么类型的细胞拥有它，以及是否 它的水平在淀粉样变组织中升高。有没有可能 SAA改变胆固醇转运活性的高密度脂蛋白将被检测。 载脂蛋白A-高密度脂蛋白与细胞或基质的相互作用 我们将探讨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.