Mitophagy: A Potential Target for Pressure Overload-Induced Cardiac Remodelling

Abstract

The pathological mechanisms underlying cardiac remodelling and cardiac dysfunction caused by pressure overload are poorly understood. Mitochondrial damage and functional dysfunction, including mitochondrial bioenergetic disorder, oxidative stress, and mtDNA damage, contribute to heart injury caused by pressure overload. Mitophagy, an important regulator of mitochondrial homeostasis and function, is triggered by mitochondrial damage and participates in the pathological process of cardiovascular diseases. Recent studies indicate that mitophagy plays a critical role in the pressure overload model, but evidence on the causal relationship between mitophagy abnormality and pressure overload-induced heart injury is inconclusive. This review summarises the mechanism, role, and regulation of mitophagy in the pressure overload model. It also pays special attention to active compounds that may regulate mitophagy in pressure overload, which provide clues for possible clinical applications.

HINT2 protects against pressure overload‐induced cardiac remodelling through mitochondrial pathways

“…Prior research links cardiac hypertrophy pathophysiology to dysfunctional complex I. Mitochondrial dysfunction, particularly involving complex I and II activity, plays a significant role in ventricular hypertrophy, heart failure and cardiac dysfunction. Mitochondrial dysfunction is associated with altered mitochondrial morphology, apoptosis initiation and cardiomyocyte loss, contributing to ventricular decompensation and the development of heart failure 33–35 . In clinical studies, a connection has been established between hypertrophic cardiomyopathy and mutations found in the NDUFS2 and NDUFV2 genes in patients undergoing clinic‐treatment 36 .…”

“…Mitochondrial dysfunction is associated with altered mitochondrial morphology, apoptosis initiation and cardiomyocyte loss, contributing to ventricular decompensation and the development of heart failure. 33 , 34 , 35 In clinical studies, a connection has been established between hypertrophic cardiomyopathy and mutations found in the NDUFS2 and NDUFV2 genes in patients undergoing clinic‐treatment. 36 In addition, progressive cardiomyopathy development is associated with heteroplasmic alterations in the mitochondrial NADH dehydrogenase 5 gene.…”