Journal of Veterinary Pharmacology and Toxicology

Cardiac fibrosis is a feature of diverse cardiovascular diseases (CVDs), contributing significantly to arrhythmias, heart failure and impaired cardiac function. It is characterized by extreme deposition of extracellular matrix (ECM), particularly collagen, which disrupts normal myocardial structure and function. A growing body of evidence implicates the NLRP3 inflammasome—a cytosolic multiprotein complex involved in innate immunity—asacentralmediator of inflammation-drivenfibrotic remodeling.ActivationofNLRP3inflammasomepromotes the maturation of pro-inflammatory cytokines IL-18 and IL-β, and induces pyroptosis, further amplifying tissue injury and fibrotic signaling. This inflammasome has been linked to fibrosis in various cardiac conditions, including myocardial infarction, atrial fibrillation, hypertension, and diabetic cardiomyopathy. Mechanistically, NLRP3 activation facilitates fibroblast-to-myofibroblast differentiation, ECM accumulation, and a dysregulated balance of matrix metalloproteinases. Therapeutic inhibition of NLRP3 inflammasome using agents such as MCC950, CY-09, and natural compounds like emodin and triptolide has demonstrated promise in attenuating fibrosis and restoring cardiac function in preclinical models. This review highlights the pathophysiological part of NLRP3 in cardiac fibrosis and explores the potential of NLRP3-targeted interventions as emerging anti-fibrotic strategies.