Regulatory Mechanisms of the NLRP3 Inflammasome, a Novel Immune-Inflammatory Marker in Cardiovascular Diseases

Abstract

The nod-like receptor family pyrin domain containing 3 (NLRP3) is currently the most widely studied inflammasome and has become a hot topic of recent research. As a macromolecular complex, the NLRP3 inflammasome is activated to produce downstream factors, including caspase-1, IL-1β, and IL-18, which then promote local inflammatory responses and induce pyroptosis, leading to unfavorable effects. A growing number of studies have examined the relationship between the NLRP3 inflammasome and cardiovascular diseases (CVDs). However, some studies have shown that the NLRP3 inflammasome is not involved in the occurrence of certain diseases. Therefore, identifying the mechanism of action of the NLRP3 inflammasome and its potential involvement in the pathological process of disease progression is of utmost importance. This review discusses the mechanisms of NLRP3 inflammasome activation and the relationship between the inflammasome and CVDs, including coronary atherosclerosis, myocardial ischemia/reperfusion, cardiomyopathies, and arrhythmia, as well as CVD-related treatments.

Keywords: NLRP3 inflammasome; cardiovascular diseases; coronary atherosclerosis; immune-inflammatory; myocardial ischemia/reperfusion.

Figure 1

NLRP3 inflammasome and associated cardiovascular diseases.

Figure 2

Activation modes of the NLRP3 inflammasome and the regulatory mechanism of CVDs. Activation of NLRP3 (1) ROS mode; (2) the ATP mode; (3) lysosome mode. Autophagy and the NLRP3 inflammasome inhibit each other, and mitochondrial autophagy inhibits the NLRP3 inflammasome. The NLRP3 inflammasome and CVDs: (a) after activation of the NLRP3 inflammasome, endothelial cells are damaged resulting in coronary atherosclerosis; (b) myocardial fibrosis is induced by the TGF-β1/Smad pathway; (c) caspase-1 mediated pyroptosis, leading to diabetic MI/R; (d) IL-18 and IL-1β can cause myocardial inflammation, coronary arteritis and myocardial hypertrophy; (e) the NLRP3 inflammasome leads to atrial fibrillation by influencing Kv1.5 and SR Ca²⁺ leakage; (f) NLRP3 deficiency induces cardiac remodeling via the TLR4/NF-κB pathway; (g) activation of the CaSR/NLRP3 inflammasome pathway leads to cardiac remodeling after MI. DADs, delayed after depolarization; APD, action potential duration.