VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA.
Johnson Center for Critical Care Medicine Pulmonary Research, Virginia Commonwealth University, Richmond, VA.
J Cardiovasc Pharmacol. 2019 Sep;74(3):175-187. doi: 10.1097/FJC.0000000000000717.
Acute myocardial infarction (AMI) is associated with the induction of a sterile inflammatory response that leads to further injury. The NACHT, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome is a macromolecular structure responsible for the inflammatory response to injury or infection. NLRP3 can sense intracellular danger signals, such as ischemia and extracellular or intracellular alarmins during tissue injury. The NLRP3 inflammasome is primed and triggered by locally released damage-associated molecular patterns and amplifies the inflammatory response and cell death through caspase-1 activation. Here, we examine the scientific evidence supporting a role for NLRP3 in AMI and the available strategies to inhibit the effects of the inflammasome. Our focus is on the beneficial effects seen in experimental models of AMI in preclinical animal models and the initial results of clinical trials.
急性心肌梗死(AMI)与无菌性炎症反应的诱导有关,而后者会导致进一步的损伤。NACHT、富含亮氨酸重复序列和pyrin 结构域蛋白 3(NLRP3)炎性小体是一种负责对损伤或感染产生炎症反应的大分子结构。NLRP3 可以感知细胞内的危险信号,例如组织损伤时的缺血和细胞外或细胞内警报素。NLRP3 炎性小体通过局部释放损伤相关分子模式而被预先激活和触发,并通过半胱天冬酶-1 的激活来放大炎症反应和细胞死亡。在这里,我们检查了支持 NLRP3 在 AMI 中的作用的科学证据,以及抑制炎性小体作用的可用策略。我们的重点是在 AMI 的实验模型中观察到的有益效果,以及在临床前动物模型和临床试验的初步结果中。