NLRP3 inflammasome expression in peripheral blood monocytes of coronary heart disease patients and its modulation by rosuvastatin

摘要

Nucleotide-binding oligomerization domain, leucine rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome has been implicated in a series of physiological and pathological processes. However, its correlation in coronary heart disease (CHD) still remains to be elucidated. The present study aimed to determine the expression of NLRP3 inflammasome in peripheral blood monocytes (PBMCs) of stable angina pectoris (SAP) and acute myocardial infarction (AMI) patients. In addition, the effect of rosuvastatin on their activities was analyzed in vitro. A total of 60 participants with SAP (n=20), AMI (n=20) and non-CHD controls (n=20) were enrolled. Fluorescence-activated cell sorting, real-time PCR, western blotting and enzyme-linked immunosorbent assay were performed to reveal the role of NLRP3 inflammasome. NLRP3 inflammasome was expressed in the PBMCs, and revealed an increased expression along the downstream interleukin (IL)-1β and IL-18 in both SAP and AMI groups, compared to the control group. Moreover, there was a more marked increase in the expression of these indicators in AMI patients when compared to SAP patients. Interference with rosuvastatin in vitro revealed that the expression of NLRP3 inflammasome and its downstream cytokines were significantly downregulated in both SAP and AMI groups in a time-dependent manner. The activation of NLRP3 inflammasome may be involved in the development of CHD, and rosuvastatin could attenuate the inflammatory process of atherosclerosis by downregulating NLRP3 expression and its downstream mediators. These findings indicated a potential role of NLRP3 in the pathogenesis and management of CHD, and also provided new insights into the mechanistic framework of rosuvastatin activity.