NLRP3 Inflammasome: Key Role in the Pathophysiology of Cardiac Disorders and its Potential as a Therapeutic Target

Abstract

Abstract: The NLRP3 inflammasome holds a pivotal position in the pathophysiological landscape of cardiac disorders, presenting itself as a promising therapeutic target. Central to this role are the proinflammatory cytokines Interleukin (IL)-1 and IL-18, which emerge as major players orchestrated by the activation of the NLRP3 inflammasome. This activation culminates in pyroptosis, a programmed form of cell death. While controlled activation of NLRP3 supports tissue repair, its excessive activation yields adverse consequences. Within the spectrum of cardiovascular diseases, ranging from abdominal aortic aneurysm to calcific aortic valve disease, the NLRP3 inflammasome is notably implicated. Atherosclerosis, myocardial infarction, diabetic cardiomyopathy, heart failure, and dilated cardiomyopathy collectively contribute to the genesis of inflammatory conditions. Key to this process is the nucleotide oligomerization domain-containing leucine-rich repeat protein 3 (NLRP3) inflammation, necessitating both priming and activation signals to orchestrate inflammation. Extensive scientific evidence substantiates the critical role of the NLRP3 inflammasome in cardiac disorders. Experimental models and clinical studies converge, highlighting its contribution to the intricate web of inflammatory pathways that underlie cardiac pathologies. This deeper understanding has spurred interest in targeting the NLRP3 inflammasome as a therapeutic avenue. Efforts to modulate the NLRP3 inflammasome are underway, aiming to temper its hyperactivity without disrupting its beneficial functions. Strategies involve small molecule inhibitors and biological agents, targeting various points along the signaling cascade. By selectively intervening in the NLRP3 pathway, researchers aspire to mitigate inflammatory responses, potentially ameliorating the progression of cardiac disorders. In conclusion, the NLRP3 inflammasome is a central orchestrator in the pathophysiology of diverse cardiac disorders. Its dual nature, capable of both driving repair and provoking harm, accentuates its significance as a therapeutic target. Scientific endeavors are actively unraveling its complexities, fostering the development of innovative interventions that could potentially revolutionize the management of cardiac inflammatory conditions.