Figure 6. Molecular and subcellular events leading to apoptosis and calcification. ETC: electron transport chain; ROS: reactive oxygen species; ER: endoplasmic reticulum; mPTP: mitochondrial permeability transition pore; LRRK2: leucine-rich repeat kinase 2; DRP1: dynamin-related protein-1. Hypoxia and ER stress had been known as the key factors in calcium overflow. ETC dysfunction and ROS reaction induced the opening of mPTP pores to release of Cyt-C which was thought to be important in the apoptotic process. DRP1 and LRRK2 were two major dysregulated genes in CAVS patients and may be used as potential therapeutic targets for microRNAs. The main of our findings have revealed the critical roles of miRNAs in the regulation of target genes that influence the mitochondrial function and muscle cell death. Concomitant with the overflow of calcium ions, the calcification of biological process was induced to activate. Therefore, hypoxia and calcification formed a vicious-loop in cardiovascular disease, exacerbating stenosis and calcification of heart valves.