Inhibitors of NLRP3 Inflammasome in Ischemic Heart Disease: Focus on Functional and Redox Aspects

Abstract

Myocardial ischemia-reperfusion injury (MIRI) is caused by several mechanisms, including the production of reactive oxygen species (ROS), altered cellular osmolarity, and inflammatory response. Calcium overload, altered oxygen levels, and mitochondrial ROS are also involved in these MIRI processes, resulting in the irreversible opening of the mitochondrial permeability transition pore (mPTP). These mechanisms and processes are associated with NLRP3 inflammasome priming and activation, which can also induce cell death by pyroptosis through the up-regulation of the caspase-1 pathway and IL-18 release. In addition, endothelial dysfunction, both in the presence and absence of MIRI, is also accompanied by altered oxygen levels, decreased nitric oxide production, and ROS overproduction, resulting in the expression of adhesion molecules and leukocyte infiltration in which the NLRP3 inflammasome plays a central role, thus contributing, through endothelial dysfunction, to the alteration of coronary flow, typical of ischemic heart disease. Given the intricate interrelationship between ROS and NLRP3, ROS inhibitors can reduce NLRP3 inflammasome activation, while NLRP3 inhibitors can reduce oxidative stress and inflammation. NLRP3 inhibitors have been intensively studied as anti-inflammatory agents in basic cardiovascular sciences. In this review, we analyze the interrelation between ROS and NLRP3 in ischemic heart disease and the effects of some NLRP3 inhibitors as possible therapeutic agents in this disease condition. All compounds considered in this review need larger studies to confirm their appropriate use in clinical scenarios as anti-ischemic drugs.

Identification of potential biomarkers associated with CD4+ T cell infiltration in myocardial ischemia-reperfusion injury using bioinformation analysis

“…The pathophysiological mechanisms of myocardial ischemia-reperfusion injury are complex, but progress is being made in this area of research to explore more effective preventive and therapeutic approaches to achieve the goal of mitigating the impact of myocardial reperfusion injury on heart health. Existing research findings are mainly related to inflammatory responses, oxidative stress, and calcium overload ( 20 - 22 ). Researchers are also currently exploring new approaches such as the use of antioxidants, inhibition of inflammatory responses, stem cell therapy or gene therapy to protect cardiomyocytes ( 23 - 25 ).…”

Apelin‐13 alleviates osteoclast formation and osteolysis through Nrf2‐pyroptosis pathway

“…Studies have shown that ROS promote tissue inflammation and activation of the NLRP3 complex in various organs. Strikingly, ROS inhibitors can reduce the activation of NLRP3 (Pagliaro & Penna, 2023). Recent study has implied that tricalcium phosphate particles promote calvarial osteocyte pyroptosis through the ROS/NLRP3/caspase-1 pathway to promote osteoclastogenesis (Zhang et al, 2022).…”