The Role of NLRP3 Inflammasome in Cardiovascular Diseases

Introduction:

NLRP3 (NACHT, LRR, and PYD domains-containing protein 3) inflammasome is a cytosolic protein complex involved in the pathogenesis of atherosclerosis . After the endothelial NLRP3 inflammasome is activated by intracellular cholesterol crystals, it directly produces endothelial dysfunction and may initiate or exacerbate vascular injuryduring hypercholesterolemia. In addition, an assembled inflammasome promotes the maturation and release of proinflammatory cytokines interleukin-1β (IL-1 β) and IL-18 .

IL-1β and IL-18 act as mediators that promote the cascade release of other cytokines. These interleukins have been previously implicated in the pathogenesis of atherosclerosis . 

Wang et al found that NLRP3 and downstream cytokines are correlated with the severity of coronary artery disease (CAD).The NLRP3 inflammasome is up-regulated within the myocardium after myocardial infarction(MI), primarily in non-cardiomyocytes (i.e. fibroblasts). Its deficiency markedly improves myocardial function and reduces infarct size after ex vivo myocardial ischaemia–reperfusion (I/R) injury. It was Sandanger  who suggested that the NLRP3 inflammasome is up-regulated in myocardial fibroblasts after MI, potentially contributing to infarct size after myocardial I/R.