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

Abstract

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.

The Inflammasome Signaling Pathway Is Actively Regulated and Related to Myocardial Damage in Coronary Thrombi from Patients with STEMI

“…Statins are suspected to mediate some of their effects through modulating inflammatory responses. Rosuvostatin was shown to attenuate the expression of NLRP3-inflammasome-related markers in circulating monocytes from patients with coronary atherosclerotic disease [ 37 ]. In another setting, in patients with ARDS [ 38 ], rosuvostatin was shown to associate with elevation in plasma IL-18 levels.…”

The Role of NLRP3 Inflammasome in Radiation-Induced Cardiovascular Injury

“…Active atherosclerotic plaques exhibit higher expression of NLRP3 inflammasome components than stable atherosclerotic plaques (Paramel Varghese et al, 2016). In addition, patients with acute coronary syndrome showed significantly increased NLRP3 expression in peripheral blood monocytes, which was directly associated with the severity of the disease (Zhu et al, 2019).…”

NLRP3 inflammasome in cardiovascular diseases: Pathophysiological and pharmacological implications

“…Subsequently, the chronicization of phlogistic processes, involving inflammasome activation, contributes to the onset of severe complications, including adverse malignant ventricular arrhythmias, left ventricular remodeling, and HF 7 . Indeed, clinical studies have documented an increased expression of NLRP3 and downstream increments of IL‐1β and IL‐18 cytokine levels in peripheral blood monocytes from MI patients 9,13,44,45 . Moreover, the NLRP3 rs35829419 variant, regarded as a gain‐of‐function polymorphism that enhances the processing and release of IL‐1β, has been associated with an increased susceptibility to develop MI in diabetic patients, thus confirming an involvement of NLRP3 pathways in MI and related complications 81 …”

“…Altaf et al 13 reported that the treatment of patients with acute MI and unstable angina with rosuvastatin was associated with a significant decrease in mRNA levels of NLRP3, cathepsin‐B, IL‐1β, and IL‐18 in peripheral monocytes. Zhu et al 44 reported that the incubation of rosuvastatin to cultures of peripheral blood monocytes inhibited the inflammasome activation, by decreasing NLRP3, ASC, and caspase‐1 expression with consequent inhibition of IL‐1β release, pointing out that statins inhibit directly NLRP3 activation.…”