Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
BMC Med. 2014 Mar 18;12:47. doi: 10.1186/1741-7015-12-47.
Immunologic research into pathogenic mechanisms operating in autoimmune-mediated atherosclerosis initially focused on adaptive immunity. Current interest is directed to more basic inflammatory mechanisms. Chronic inflammation (innate immunity-associated) may trigger initial events that can lead to atherosclerotic cardiovascular disease. This chronic inflammation may start early in life and be perpetuated by classic atherosclerosis risk factors. Lipid peroxidation of low-density lipoprotein seems to be a key event in the initiation and progression of atherosclerosis. Oxidized low-density lipoprotein triggers inflammatory and immunogenic events that promote endothelial dysfunction and the synthesis and secretion of pro-inflammatory cytokines, leading to an autoimmune response capable of accelerating the intracellular accumulation of lipids within atherosclerotic plaques. Oxidized low-density lipoprotein binds β2-glycoprotein I to form circulating complexes found in both autoimmune and non-autoimmune atherosclerosis. It is likely that β2-glycoprotein I and/or these complexes contribute to early atherogenesis by stimulating pro-inflammatory innate immunity through endogenous sensors and inflammasome/interleukin-1 pathways. We discuss the chronic inflammatory (innate) and autoimmune (adaptive) responses operating in atherosclerosis to discern the role of autoimmunity in atherosclerotic cardiovascular disease.
免疫学生物学对自身免疫性动脉粥样硬化发病机制的研究最初集中在适应性免疫上。目前的研究兴趣集中在更基本的炎症机制上。慢性炎症（与固有免疫相关）可能引发最初的事件，导致动脉粥样硬化性心血管疾病。这种慢性炎症可能很早就开始，并被经典的动脉粥样硬化危险因素所延续。低密度脂蛋白的脂质过氧化似乎是动脉粥样硬化发生和发展的关键事件。氧化的低密度脂蛋白触发炎症和免疫原性事件，导致内皮功能障碍以及促炎细胞因子的合成和分泌，从而引发能够加速动脉粥样硬化斑块内脂质细胞内积累的自身免疫反应。氧化的低密度脂蛋白与β2-糖蛋白 I 结合形成循环复合物，在自身免疫和非自身免疫性动脉粥样硬化中都有发现。β2-糖蛋白 I 和/或这些复合物可能通过内源性传感器和炎症小体/白细胞介素-1 途径刺激促炎固有免疫，从而促进早期动脉粥样硬化形成。我们讨论了在动脉粥样硬化中起作用的慢性炎症（固有）和自身免疫（适应性）反应，以辨别自身免疫在动脉粥样硬化性心血管疾病中的作用。
