Mitochondrial contributions to vascular endothelial dysfunction, arterial stiffness, and cardiovascular diseases

Cardiovascular disease (CVD) affects one in three adults and remains the leading cause of death in America. Advancing age is a major risk factor for CVD. Recent plateaus in CVD-related mortality rates in high-income countries after decades of decline highlight a critical need to identify novel therapeutic targets and strategies to mitigate and manage the risk of CVD development and progression. Vascular dysfunction, characterized by endothelial dysfunction and large elastic artery stiffening, is independently associated with an increased CVD risk and incidence and is therefore an attractive target for CVD prevention and management. Vascular mitochondria have emerged as an important player in maintaining vascular homeostasis. As such, age- and disease-related impairments in mitochondrial function contribute to vascular dysfunction and consequent increases in CVD risk. This review outlines the role of mitochondria in vascular function and discusses the ramifications of mitochondrial dysfunction on vascular health in the setting of age and disease. The adverse vascular consequences of increased mitochondrial-derived reactive oxygen species, impaired mitochondria! quality control, and defective mitochondria! calcium cycling are emphasized, in particular. Current evidence for both lifestyle and pharmaceutical mitochondrial-targeted strategies to improve vascular function is also presented.

Automated summary

Cardiovascular disease is a leading cause of death in America, with advancing age being a major risk factor. Vascular dysfunction, characterized by endothelial dysfunction and large elastic artery stiffening, is associated with an increased CVD risk. Mitochondria play a crucial role in maintaining vascular homeostasis, and age- and disease-related impairments in mitochondrial function contribute to vascular dysfunction and increase CVD risk.