VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA 23298, USA.
Pharmacotherapy and Outcomes Sciences, Virginia Commonwealth University, Richmond, VA 23298, USA.
Molecules. 2021 Feb 12;26(4):976. doi: 10.3390/molecules26040976.
Virtually all types of cardiovascular diseases are associated with pathological activation of the innate immune system. The NACHT, leucine-rich repeat (LRR), and pyrin domain (PYD)-containing protein 3 (NLRP3) inflammasome is a protein complex that functions as a platform for rapid induction of the inflammatory response to infection or sterile injury. NLRP3 is an intracellular sensor that is sensitive to danger signals, such as ischemia and extracellular or intracellular alarmins during tissue injury. The NLRP3 inflammasome is regulated by the presence of damage-associated molecular patterns and initiates or amplifies inflammatory response through the production of interleukin-1β (IL-1β) and/or IL-18. NLRP3 activation regulates cell survival through the activity of caspase-1 and gasdermin-D. The development of NLRP3 inflammasome inhibitors has opened the possibility to targeting the deleterious effects of NLRP3. Here, we examine the scientific evidence supporting a role for NLRP3 and the effects of inhibitors in cardiovascular diseases.
几乎所有类型的心血管疾病都与固有免疫系统的病理性激活有关。NACHT、富含亮氨酸重复序列(LRR)和pyrin 结构域(PYD)的蛋白 3(NLRP3)炎性小体是一种蛋白质复合物,作为对感染或无菌损伤的炎症反应的快速诱导的平台。NLRP3 是一种细胞内传感器,对危险信号敏感,如组织损伤时的缺血和细胞外或细胞内警报素。NLRP3 炎性小体受损伤相关分子模式的存在调节,并通过白细胞介素-1β(IL-1β)和/或 IL-18 的产生来启动或放大炎症反应。NLRP3 的激活通过半胱天冬酶-1 和 gasdermin-D 的活性调节细胞存活。NLRP3 炎性小体抑制剂的开发为靶向 NLRP3 的有害作用开辟了可能性。在这里,我们检查了支持 NLRP3 作用的科学证据以及抑制剂在心血管疾病中的作用。