Role of PTEN-Induced Protein Kinase 1 as a Mitochondrial Dysfunction Regulator in Cardiovascular Disease Pathogenesis

Abstract

Cardiovascular disease (CVD) remains a global health challenge, primarily due to atherosclerosis, which leads to conditions such as coronary artery disease, cerebrovascular disease, and peripheral arterial disease. Mitochondrial dysfunction initiates endothelial dysfunction, a key contributor to CVD pathogenesis, as well as triggers the accumulation of reactive oxygen species (ROS), energy stress, and cell death in endothelial cells, which are crucial for atherosclerosis development. This review explores the role of PTEN-induced protein kinase 1 (PINK1) in mitochondrial quality control, focusing on its significance in cardiovascular health. PINK1 plays a pivotal role in mitophagy (selective removal of damaged mitochondria), contributing to the prevention of CVD progression. PINK1-mediated mitophagy also affects the maintenance of cardiomyocyte homeostasis in ischemic heart disease, thus mitigating mitochondrial dysfunction and oxidative stress, as well as regulates endothelial health in atherosclerosis through influencing ROS levels and inflammatory response. We also investigated the role of PINK1 in vascular smooth muscle cells, emphasizing on its role in apoptosis and atherosclerosis. Dysfunctional mitophagy in these cells accelerates cellular senescence and contributes to adverse effects including plaque rupture and inflammation. Mitophagy has also been explored as a potential therapeutic target for vascular calcification, a representative lesion in atherosclerosis, with a focus on lactate-induced mechanisms. Finally, we highlight the current research and clinical trials targeting mitophagy as a therapeutic avenue for CVD.

Keywords

• cardiovascular disease
• pten-induced protein kinase 1
• endothelial dysfunction
• mitophagy
• vascular calcification