From Injury to Heart Failure: Molecular and Cellular Mechanisms of Ischemia-Reperfusion Injury
Main Article Content
Abstract
Background: Myocardial ischemia-reperfusion injury (IRI) represents a significant clinical challenge, contributing to cardiomyocyte death and adverse cardiovascular outcomes. Despite advances in therapeutic strategies, the molecular mechanisms driving IRI remain incompletely understood, hindering the development of effective interventions.
Objective: This review aims to provide a comprehensive overview of the molecular and cellular mechanisms underlying myocardial IRI, emphasizing the roles of programmed cell death pathways, inflammasomes, interleukins, and the intricate balance of autophagy in cardiac injury and repair.
Key Findings: Apoptosis, pyroptosis, and necroptosis contribute to cardiomyocyte death, each characterized by distinct morphological and biochemical features. These pathways are intricately regulated by signaling molecules such as caspases, gasdermin D, and receptor-interacting protein kinases. Activation of the NLRP3 inflammasome and subsequent production of interleukins such as IL-1β and IL-18 exacerbate the inflammatory response, driving further myocardial damage. These pathways are linked to adverse cardiac remodeling and chronic cardiovascular diseases, including heart failure and atherosclerosis. Functional autophagy mitigates cellular stress by removing damaged organelles and misfolded proteins, limiting inflammasome activation. Dysregulated autophagy, however, amplifies cardiac injury during ischemia-reperfusion injury. Targeting these pathways through pharmacological agents such as inflammasome inhibitors, interleukin blockers, and autophagy modulators holds promise for mitigating IRI and improving cardiac outcomes.
Conclusions: A deeper understanding of these molecular mechanisms offers a roadmap for developing targeted interventions to prevent and treat myocardial ischemia-reperfusion injury. Translational efforts focusing on these pathways may enhance therapeutic efficacy and reduce the burden of cardiovascular diseases. Advancing preclinical research and clinical trials is crucial to address knowledge gaps and overcome translational barriers. Integrating molecular insights into personalized therapeutic approaches may redefine the management of myocardial IRI and its long-term sequelae.
Article Details
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