NLRP3 inflammasome: Its regulation and involvement in atherosclerosis

• Published in: Journal of cellular physiology Vol. 233; no. 3; pp. 2116 - 2132
• Main Authors: Hoseini, Zahra, Sepahvand, Fatemeh, Rashidi, Bahman, Sahebkar, Amirhossein, Masoudifar, Aria, Mirzaei, Hamed
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.03.2018
• Subjects: Apoptosis; Apoptosis - genetics; Apoptosis - physiology; Arteriosclerosis; Atherogenesis; Atherosclerosis; Atherosclerosis - pathology; Calcium Signaling - physiology; Caspase; Caspase-1; Cell activation; Cholesterol; Cholesterol - metabolism; Endoplasmic reticulum; Endoplasmic Reticulum Stress - physiology; Enzyme Activation - physiology; Humans; Immunity; inflammasome; Inflammasomes; Inflammation - pathology; Innate immunity; Interleukin 1; Interleukin 18; Interleukin-18 - metabolism; Interleukin-1beta - metabolism; Intracellular; JNK protein; Lipid metabolism; Lipid Metabolism - physiology; Lipoproteins, LDL - metabolism; Low density lipoprotein; Macrophages; Macrophages - physiology; MAP kinase; MAP Kinase Kinase Kinase 5 - metabolism; Metabolism; MicroRNAs - genetics; miRNA; Mitochondria; Mitochondria - pathology; Mitogen-Activated Protein Kinase 8 - metabolism; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3; Oxidative stress; Plaques; Pyroptosis; Pyroptosis - physiology; Reactive oxygen species; Regulators; Ribonucleic acid; RNA; signaling pathway; atherosclerosis; signaling pathway; NLRP3; inflammasome
• ISSN: 0021-9541; 1097-4652; 1097-4652
• DOI: 10.1002/jcp.25930

Inflammasomes are intracellular complexes involved in the innate immunity that convert proIL‐1β and proIL‐18 to mature forms and initiate pyroptosis via cleaving procaspase‐1. The most well‐known inflammasome is NLRP3. Several studies have indicated a decisive and important role of NLRP3 inflammasome, IL‐1β, IL‐18, and pyroptosis in atherosclerosis. Modern hypotheses introduce atherosclerosis as an inflammatory/lipid‐based disease and NLRP3 inflammasome has been considered as a link between lipid metabolism and inflammation because crystalline cholesterol and oxidized low‐density lipoprotein (oxLDL) (two abundant components in atherosclerotic plaques) activate NLRP3 inflammasome. In addition, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and lysosome rupture, which are implicated in inflammasome activation, have been discussed as important events in atherosclerosis. In spite of these clues, some studies have reported that NLRP3 inflammasome has no significant effect in atherogenesis. Our review reveals that some molecules such as JNK‐1 and ASK‐1 (upstream regulators of inflammasome activation) can reduce atherosclerosis through inducing apoptosis in macrophages. Notably, NLRP3 inflammasome can also cause apoptosis in macrophages, suggesting that NLRP3 inflammasome may mediate JNK‐induced apoptosis, and the apoptotic function of NLRP3 inflammasome may be a reason for the conflicting results reported. The present review shows that the role of NLRP3 in atherogenesis can be significant. Here, the molecular pathways of NLRP3 inflammasome activation and the implications of this activation in atherosclerosis are explained. Inflammasomes are known as intracellular complexes which are able to convert pro‐IL‐1β and proIL‐18 to mature forms and initiate pyroptosis through cleaving pro‐caspase‐1. NLRP3 is a well‐known inflammasome which has central roles in atherosclerosis. It has been shown that NLRP3 inflammasome contributes to the progression of atherosclerosis via affecting a sequence of cellular and molecular targets such as STAT, MAPK, JNK, microRNA network, ROS, and PKR.