Division of Cardiovascular Medicine, University of Cambridge, Box 110, ACCI, Addenbrooke's Hospital, Cambridge CB2 2QQ, United Kingdom.
Arterioscler Thromb Vasc Biol. 2011 Dec;31(12):2781-6. doi: 10.1161/ATVBAHA.111.224907.
Cell death and inflammation are ancient processes of fundamental biological importance in both normal physiology and pathology. This is evidenced by the profound conservation of mediators, with ancestral homologues identified from plants to humans, and the number of diseases driven by aberrant control of either process. Apoptosis is the most well-studied cell death, but many forms exist, including autophagy, necrosis, pyroptosis, paraptosis, and the obscure dark cell death. Cell death occurs throughout the cardiovascular system, from initial shaping of the heart and vasculature during development to involvement in pathologies, including atherosclerosis, aneurysm, cardiomyopathy, restenosis, and vascular graft rejection. However, determining whether cell death primarily drives pathology or is a secondary bystander effect is difficult. Inflammation, the primary response of innate immunity, is considered essential in initiating and driving vascular diseases. Cell death and inflammation are inextricably linked with their effectors modulating the other process. Indeed, an evolutionary link between cell death and inflammation occurs at caspase-1 (which activates interleukin-1β), which can induce death by pyroptosis, and is a member of the caspase family vital for apoptosis. This review examines cell death in vascular disease, how it can induce inflammation, and finally the emergence of inflammasomes in vascular pathology.
细胞死亡和炎症是正常生理和病理过程中具有基础生物学重要性的古老过程。这一点可以从介质的深刻保守性得到证明，从植物到人类都可以识别出祖先同源物，并且由于这两个过程的异常控制而导致的疾病数量众多。细胞凋亡是研究最深入的细胞死亡形式，但还存在许多其他形式，包括自噬、坏死、细胞焦亡、Paraptosis 和暗细胞死亡。细胞死亡发生在心血管系统的各个部位，从心脏和脉管系统在发育过程中的最初形成到参与动脉粥样硬化、动脉瘤、心肌病、再狭窄和血管移植物排斥等病理过程。然而，确定细胞死亡是主要驱动病理过程还是作为继发性旁观者效应，这一点很困难。炎症是先天免疫的主要反应，被认为是启动和驱动血管疾病的关键。细胞死亡和炎症是紧密相连的，它们的效应器相互调节。事实上，细胞死亡和炎症之间存在着进化上的联系，这种联系发生在半胱天冬酶-1（激活白细胞介素-1β）上，它可以通过细胞焦亡诱导细胞死亡，而半胱天冬酶-1是凋亡过程中至关重要的半胱天冬酶家族的成员。这篇综述考察了血管疾病中的细胞死亡，以及它如何引发炎症，最后还考察了炎症小体在血管病理学中的出现。
