title: NLRP3 inflammasome: Its regulation and involvement in atherosclerosis.
abstract: 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.
authors.affiliation: Faculty of Medicine, Students Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Hoseini
authors.affiliation: Faculty of Medicine, Students Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Sepahvand
authors.affiliation: Department of Anatomical Sciences and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Bahman
authors.initials: B
authors.lastname: Rashidi
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Sahebkar
authors.affiliation: Department of Molecular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
authors.forename: Aria
authors.initials: A
authors.lastname: Masoudifar
authors.affiliation: Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Hamed
authors.identifier: http://orcid.org/0000-0002-9399-8281
authors.initials: H
authors.lastname: Mirzaei
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D050197:Atherosclerosis / Q000473:pathology*; D020013:Calcium Signaling / Q000502:physiology; D002784:Cholesterol / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology; D008077:Lipoproteins, LDL / Q000378:metabolism; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D008264:Macrophages / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics; D008928:Mitochondria / Q000473:pathology; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D000069292:Pyroptosis / Q000502:physiology
chemical_list: C508585:IL1B protein, human; D020382:Interleukin-18; D053583:Interleukin-1beta; D008077:Lipoproteins, LDL; D035683:MicroRNAs; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C099252:oxidized low density lipoprotein; D002784:Cholesterol; D048055:Mitogen-Activated Protein Kinase 8; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human
keywords: NLRP3; atherosclerosis; inflammasome; signaling pathway