Ji Ailing, Meredith Luke W, Shridas Preetha
Saha Cardiovascular Research Center, University of Kentucky, 567 Charles T Wethington Building, 900 S. Limestone Street, Lexington, KY 40536-0200, USA.
Department of Internal Medicine, University of Kentucky, 567 Charles T Wethington Building, 900 S. Limestone Street, Lexington, KY 40536-0200, USA.
Int J Mol Sci. 2025 May 9;26(10):4528. doi: 10.3390/ijms26104528.
Despite more than fifty years since its discovery in the 1970s, Serum Amyloid A (SAA)'s true biological functions remain enigmatic. The research so far has primarily associated SAA with chronic inflammatory conditions such as cardiovascular disease, obesity, and type 2 diabetes; its role in acute inflammation is less understood. Unlike the modest elevations observed in chronic conditions, SAA levels surge dramatically during acute inflammatory responses. Notably, approximately 2.5% of hepatic protein synthesis is devoted to SAA production during acute inflammation-despite the high energy demands required for synthesizing pro-inflammatory cytokines and immune cell activation-leaving its precise necessity unclear. Elucidating SAA's physiological role in acute inflammation is crucial to determine the therapeutic potential of SAA inhibition for chronic inflammatory diseases, such as atherosclerosis and abdominal aortic aneurysms. The evidence suggests that SAA may play a protective role in acute inflammation, positioning it as a "double-edged sword": detrimental in chronic inflammation, yet potentially beneficial in acute settings. This review explores the divergent roles of SAA in chronic versus acute inflammation, proposing that while SAA inhibition could offer therapeutic benefits for chronic conditions, it might pose risks during acute inflammation. As the primary transporter of SAA in circulation, high-density lipoprotein (HDL) has been shown to become dysfunctional in chronic inflammation, at least partly due to SAA's effects. However, we propose that SAA may confer functional properties to HDL during acute inflammatory states, such as sepsis, thereby highlighting the context-dependent nature of its impact.
尽管血清淀粉样蛋白A（SAA）自20世纪70年代被发现以来已有五十多年，但它真正的生物学功能仍然成谜。迄今为止的研究主要将SAA与慢性炎症性疾病联系起来，如心血管疾病、肥胖症和2型糖尿病；而其在急性炎症中的作用则了解较少。与在慢性疾病中观察到的适度升高不同，SAA水平在急性炎症反应期间会急剧飙升。值得注意的是，在急性炎症期间，尽管合成促炎细胞因子和激活免疫细胞需要大量能量，但肝脏蛋白质合成中约2.5%用于SAA的产生，这使得其确切必要性尚不清楚。阐明SAA在急性炎症中的生理作用对于确定抑制SAA对动脉粥样硬化和腹主动脉瘤等慢性炎症性疾病的治疗潜力至关重要。有证据表明，SAA可能在急性炎症中发挥保护作用，这使其成为一把“双刃剑”：在慢性炎症中有害，但在急性情况下可能有益。本综述探讨了SAA在慢性炎症与急性炎症中的不同作用，提出虽然抑制SAA可能对慢性疾病有治疗益处，但在急性炎症期间可能会带来风险。作为循环中SAA的主要转运蛋白，高密度脂蛋白（HDL）已被证明在慢性炎症中功能失调，至少部分是由于SAA的影响。然而，我们提出，在急性炎症状态（如脓毒症）下，SAA可能赋予HDL功能特性，从而突出了其影响的背景依赖性。
