FUNCTION OF SERUM AMYLOID A PROTEIN (SAA)

血清淀粉样蛋白 A (SAA) 的功能

• 批准号: 3160749
• 负责人: FREDERICK C. DE BEER
• 金额: $ 17.18万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3160749
• 关键词: amyloidosis; apolipoproteins; cardiovascular disorder; disease /disorder proneness /risk; endopeptidases; enzyme induction /repression; family genetics; high density lipoproteins; human subject; inflammation; isoelectric point; lipid transport; molecular pathology; northern blottings; protein sequence; protein transport; restriction fragment length polymorphism; rheumatoid arthritis

During the acute phase response, serum amyloid A protein apolipoprotein, increases 1,000 fold, and becomes a major component of HDL. In spite of intense modern interest in the HDL particle, the teleological role of this alteration of HDL by SAA in acute inflammation is unknown. We propose that a major role may be facilitation of delivery by HDL of needed phospholipid in peripheral sites of inflammation, where consumption of phospholipid in cell membrane destruction, prostonoid synthesis and the phosphatidyl inositol cell activation pathway is considerable. Chronic persistence of A-SAA render HDL less capable of mediating reverse cholesterol transport and provides a molecular explanation for the increased mortality of patients with chronic active rheumatoid arthritis from particularly cardiovascular disease. In addition to acute phase SAA (A-SAA), we have characterized a new SAA subfamily constitutive on normal HDL (C-SAA). This establishes the existence of a SAA superfamily with two distinct subfamilies. We propose that the C-SAA subfamily play a role in the normal biological function of HDL in that it promotes reverse cholesterol transport by causing the degradation of apo-AII. We will investigate whether during inflammation, aberrant induction of C-SAA might cause pathological neutral protease release with destructive potential. The studies proposed will extend our understanding of the physiologic role of the SAA's in inflammation and may help explain the propensity to advanced atherosclerosis in patients with chronic inflammatory rheumatic diseases.

在急性期反应中，血清淀粉样蛋白A蛋白、载脂蛋白、 增加了1000倍，成为高密度脂蛋白的主要组成部分。尽管 现代对高密度脂蛋白粒子的浓厚兴趣，目的论的作用 SAA在急性炎症中对高密度脂蛋白的这种改变是未知的。我们 提出主要作用可能是促进高密度脂蛋白的交付 炎症周围部位需要磷脂， 磷脂在细胞膜破坏中的消耗，前列腺素 磷脂酰肌醇的合成和细胞激活途径 相当可观。A-SAA的慢性持续使高密度脂蛋白能力降低 介导胆固醇的反向转运，并提供一种分子 慢性活动期患者死亡率增加的原因分析 尤其是心血管疾病引起的类风湿性关节炎。在……里面 除了急性期SAA(A-SAA)外，我们还鉴定了一种新的SAA 正常高密度脂蛋白的亚家族构成(C-SAA)。这建立了 具有两个不同亚族的SAA超家族的存在性。我们建议 C-SAA亚家族在血管内皮细胞正常生物学功能中发挥作用 高密度脂蛋白是因为它通过引起 载脂蛋白AII的降解。我们将调查在炎症期间， C-SAA的异常诱导可能导致病理性中性蛋白酶 释放具有破坏性的潜力。建议的研究将延长我们的 对SAA在炎症和炎症反应中的生理作用的认识 可能有助于解释患者发生晚期动脉粥样硬化的倾向 患有慢性炎症性风湿病。