细胞焦亡在心血管疾病中的作用

Role of pyroptosis in cardiovascular diseases

细胞焦亡是一种新发现的细胞程序性死亡方式,该过程包含多种细胞因子的激活与降解。首先,细胞内炎症小体被激活,进而诱导半胱天冬酶(caspase)-1的激活和促炎症因子IL-1和IL-18前体的降解。之后,细胞膜裂解与细胞核DNA片段化可导致IL-1和IL-18释放,最终诱发炎症反应。机体固有免疫细胞经模式识别受体,识别病原相关分子模式或损伤相关分子模式,诱发细胞焦亡而清除病原体或损伤组织细胞,形成保护机体的一道有效屏障。越来越多的研究表明,在动脉粥样硬化(AS)的病理过程中,细胞焦亡不仅参与动脉粥样斑块的形成,也是促进斑块发展,甚至是影响斑块稳定性的重要因素。在心肌缺血/再灌注损伤中,细胞焦亡亦是MI区与边界区炎症反应的重要调控因子,其可影响修复期MI面积、纤维化程度与心功能。因此,细胞焦亡可能成为临床防治AS,以及促进缺血/再灌注心肌修复的新靶点。

Pyroptosis is programmed cell death characterized by activation or degradation of a series of cytokines. Intracellular inflammasomes are first activated, which induces the activation of caspase-1 and degradation of proinflammatory cytokines interleukin （IL）-Iβ and IL-18. Subsequently, disruption of cell membranes with fragmentation of nuclear DNA leads to IL-1 and IL-18 release, which finally induces inflammatory reaction. The innate immune cells of the body identify pathogen associated molecular patterns or damage associated molecular patterns via recognition receptor and then remove pathogens or damaged tissue cells by inducing pyroptosis, forming an effective barrier to protect the organism. A growing number of studies related to atherosclerosis have demonstrated that pyroptosis is not only involved in formation of atheromatous plaque, but also is a crucial factor which promotes the development and stability of plaques. In myocardial ischemia-reperfusion injury, pyroptosis is also an important regulatory factor of the inflammatory response in the myocardial infarct and border zones, which can affect myocardial infarct size, fibrosis degree and cardiac function in the repair period. In summary, pyroptosis may become a novel therapeutic target for atherosclerosis and myocardial ischemia-reperfusion injury.