Laboratory of Autoimmunity, Section for Experimental Pathophysiology and Immunology, Biocenter, Innsbruck Medical University, Peter-Mayr-Strasse 1a, 6020 Innsbruck, Austria.
Department of Radiology, Karolinska University Hospital, Karolinska Vägen, Solna 17176 Stockholm, Sweden.
Nat Rev Cardiol. 2014 Sep;11(9):516-29. doi: 10.1038/nrcardio.2014.91. Epub 2014 Jul 15.
Atherosclerosis is a chronic, multifactorial disease that starts in youth, manifests clinically later in life, and can lead to myocardial infarction, stroke, claudication, and death. Although inflammatory processes have long been known to be involved in atherogenesis, interest in this subject has grown in the past 30-40 years. Animal experiments and human analyses of early atherosclerotic lesions have shown that the first pathogenic event in atherogenesis is the intimal infiltration of T cells at arterial branching points. These T cells recognize heat shock protein (HSP)60, which is expressed together with adhesion molecules by endothelial cells in response to classic risk factors for atherosclerosis. Although these HSP60-reactive T cells initiate atherosclerosis, antibodies to HSP60 accelerate and perpetuate the disease. All healthy humans develop cellular and humoral immunity against microbial HSP60 by infection or vaccination. Given that prokaryotic (bacterial) and eukaryotic (for instance, human) HSP60 display substantial sequence homology, atherosclerosis might be the price we pay for this protective immunity, if risk factors stress the vascular endothelial cells beyond physiological conditions.
动脉粥样硬化是一种慢性、多因素疾病，始于青年时期，在生命后期才出现临床症状，并可能导致心肌梗死、中风、跛行和死亡。尽管炎症过程早已被认为与动脉粥样硬化的发生有关，但在过去 30-40 年中，人们对这一课题的兴趣日益增加。动物实验和对早期动脉粥样硬化病变的人类分析表明，动脉粥样硬化发生的第一个致病事件是 T 细胞在动脉分叉处的内膜浸润。这些 T 细胞识别热休克蛋白（HSP）60，内皮细胞在经典动脉粥样硬化风险因素的作用下共同表达 HSP60 与粘附分子。尽管这些 HSP60 反应性 T 细胞引发动脉粥样硬化，但 HSP60 抗体加速并使疾病持续存在。所有健康人都会通过感染或接种疫苗对微生物 HSP60 产生细胞和体液免疫。如果危险因素使血管内皮细胞超出生理条件，那么鉴于原核（细菌）和真核（例如人类）HSP60 显示出显著的序列同源性，动脉粥样硬化可能是我们为这种保护性免疫付出的代价。
