Figure 1.

Mitochondrial dysfunction as a cause or consequence of vascular calcification. Increased ROS generation and mineral dysregulation via damaged mitochondrial electron transport chain (ETC) complexes are the likely key cause and consequence of mitochondrial dysfunction observed during vascular calcification. (A) Calcium released from the hydroxyapatite crystals from the extracellular matrix can enter the cytoplasm via endosomes and make its way to the mitochondrial matrix causing calcium (Ca) and phosphate (Pi) overload. This calcium and phosphate overload can damage the electron transport chain complexes and generate ROS. (B) AGEs are glycotoxins which are elevated in diabetes. AGEs and the receptor for AGEs (RAGE) generate ROS from mitochondria and play a significant role in accelerating the vascular calcification process by enhanced synthesis of extracellular matrix components. Furthermore, ROS production is enhanced in aging vascular cells. (C) Enhanced ROS leads to vascular stiffening, vascular calcification, VSMC transition to osteoblast or chondrocyte-like cells and the metabolic switching from oxidative phosphorylation to glycolysis. All these pathways are commonn denominators in pathologies including calcific aortic valve disease, atherosclerosis, type-II diabetes, CKD, and ESRD.