Molecular and Pathophysiological Mechanisms Underlying Ischemic Heart Disease (IHD): An Integrative Narrative Review

Abstract

Ischemic heart disease (IHD) remains the leading global cause of morbidity and mortality, driven by a complex interplay of atherosclerosis, inflammation, endothelial dysfunction, thrombosis, and oxidative stress. Despite notable declines in mortality in high-income regions, the burden of IHD continues to rise in low- and middle-income countries, where risk factors, healthcare disparities, and environmental exposures compound disease progression. The molecular mechanisms that underlie plaque initiation, progression, and destabilization are increasingly recognized as crucial therapeutic targets. However, important gaps persist—particularly in understanding how inflammatory pathways, oxidative stress, and immune activation converge to cause myocardial injury and adverse cardiovascular events. This narrative review synthesizes current evidence on the molecular and pathophysiological basis of IHD, elaborating on atherosclerotic plaque biology, coronary artery narrowing, thrombosis development, myocardial ischemia and infarction, and the interconnected inflammatory and oxidative stress pathways central to disease evolution. Emerging therapeutic opportunities—including inflammasome inhibitors, targeted anti-inflammatory agents, endothelial modulators, and mitochondrial-protective strategies—are highlighted in relation to their potential to complement conventional lipid-lowering and antithrombotic therapy. Future research must focus on translating molecular insights into personalized treatment strategies to support earlier diagnosis, better risk stratification, and improved clinical outcomes for diverse global populations.