Abstract
Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide and is attributed to complex pathophysiological mechanisms that surpass the traditional risk factors. Emerging evidence indicates that mitochondrial dysfunction plays a central role in CVD progression, linking impaired bioenergetics, oxidative stress imbalance, and defective mitochondrial quality control to endothelial dysfunction, myocardial injury, and adverse cardiac remodeling. However, the mechanistic interplay between mitochondrial dysfunction and CVD pathogenesis remains unclear. This review provides a comprehensive synthesis of recent knowledge, focusing on the dysregulation of mitochondrial energy metabolism, alterations in mitochondrial membrane potential, and disruptions in mitochondrial dynamics, including the balance of fusion and fission, mitophagy, and biogenesis. Furthermore, we critically evaluated emerging mitochondria-targeted therapeutic strategies, including pharmacological agents, gene therapies, and regenerative approaches. By bridging fundamental mitochondrial biology with clinical cardiology, this review underscores the critical translational challenges and opportunities in developing mitochondria-focused interventions. A deeper understanding of the mitochondrial mechanisms in CVD pathophysiology will offer novel diagnostic biomarkers and precision-targeted therapeutics, thereby transforming CVD management.