FUNCTION OF SERUM AMYLOID A PROTEIN (SAA)

在急性期反应期间，血清淀粉样蛋白A蛋白载脂蛋白， 增加1,000倍，成为HDL的主要成分。尽管 强烈的现代兴趣的HDL粒子，目的论的作用， 在急性炎症中SAA对HDL的这种改变是未知的。 我们 建议，一个主要的作用可能是促进交付的HDL， 需要磷脂在周围部位的炎症，其中 细胞膜破坏中磷脂的消耗，前列腺素 合成和磷脂酰肌醇细胞活化途径， 可观 A-SAA的慢性持续性使HDL的能力降低， 介导胆固醇的逆向转运，并提供一种分子 慢性活动性心脏病患者死亡率增加的原因 类风湿性关节炎尤其是心血管疾病。 在 除了急性期SAA（A-SAA），我们还描述了一种新的SAA 正常HDL亚家族组成型（C-SAA）。 这就确立了 存在一个SAA超家族和两个不同的亚家族。 我们提出 C-SAA亚家族在正常的生物学功能中发挥作用， 高密度脂蛋白，因为它促进胆固醇逆向转运， apo-AII的降解。 我们将研究在炎症期间， C-SAA的异常诱导可能导致病理性中性蛋白酶 释放出具有破坏性的潜能。 建议的研究将扩大我们的 了解SAA在炎症中的生理作用， 可能有助于解释患者中晚期动脉粥样硬化的倾向 患有慢性炎症性风湿病

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.