Mitochondria spatially and temporally modulate VSMC phenotypes via interacting with cytoskeleton in cardiovascular diseases

Cardiovascular diseases caused by atherosclerosis (AS) seriously endanger human health, which is closely related to vascular smooth muscle cell (VSMC) phenotypes. VSMC phenotypic transformation is marked by the alteration of phenotypic marker expression and cellular behaviour. Intriguingly, the mitochondrial metabolism and dynamics altered during VSMC phenotypic transformation. Firstly, this review combs VSMC mitochondrial metabolism in three aspects: mitochondrial ROS generation, mutated mitochondrial DNA (mtDNA) and calcium metabolism respectively. Secondly, we summarized the role of mitochondrial dynamics in regulating VSMC phenotypes. We further emphasized the association between mitochondria and cytoskelton via presenting cytoskeletal support during mitochondrial dynamics process, and discussed its impact on their respective dynamics. Finally, considering that both mitochondria and cytoskeleton are mechano-sensitive organelles, we demonstrated their direct and indirect interaction under extracellular mechanical stimuli through several mechano-sensitive signaling pathways. We additionally discussed related researches in other cell types in order to inspire deeper thinking and reasonable speculation of potential regulatory mechanism in VSMC phenotypic transformation.