Mitochondrial dynamics in vascular remodeling and target-organ damage

Abstract

Vascular remodeling is the pathological basis for the development of many cardiovascular diseases. The mechanisms underlying endothelial cell dysfunction, smooth muscle cell phenotypic switching, fibroblast activation, and inflammatory macrophage differentiation during vascular remodeling remain elusive. Mitochondria are highly dynamic organelles. Recent studies showed that mitochondrial fusion and fission play crucial roles in vascular remodeling and that the delicate balance of fusion-fission may be more important than individual processes. In addition, vascular remodeling may also lead to target-organ damage by interfering with the blood supply to major body organs such as the heart, brain, and kidney. The protective effect of mitochondrial dynamics modulators on target-organs has been demonstrated in numerous studies, but whether they can be used for the treatment of related cardiovascular diseases needs to be verified in future clinical studies. Herein, we summarize recent advances regarding mitochondrial dynamics in multiple cells involved in vascular remodeling and associated target-organ damage.

Mitochondrial Dysfunction: A Roadmap for Understanding and Tackling Cardiovascular Aging

“…Interestingly, it can be hypothesized from studies of nematodes that either mitochondrial fission or impaired fusion function greatly reduces median lifespan, suggesting a potential role for mitochondrial dynamics in regulating lifespan [22]. The delicate equilibrium between fusion and fission has been proven to be more significant than the degree of each individual process [23]. Excess or untimely occurrence of fission or fusion can significantly affect mitochondrial quality and disrupt mitochondrial homeostasis [24].…”

“…Maintaining a delicate fusion-fission balance in endothelial cells is essential to prevent pathological cardiovascular changes (including heart failure, diabetic cardiomyopathy, myocardial infarction, and atherosclerosis) and vascular remodeling (including inducement of endothelial inflammatory responses, reduction of endothelial cell activity, and inhibition of angiogenesis) [23,46]. Imbalances in either fusion or fission processes are a contributing factor to the development of age-related cardiovascular diseases, such as heart failure [47].…”

“…Endothelial cells play a crucial role in angiogenesis, and impaired angiogenesis is a hallmark of vascular aging, often linked to endothelial dysfunction. Recent research suggests that altered mitochondrial dynamics in endothelial cells is a contributing factor to impaired angiogenesis, suggesting a connection between mitochondrial dynamics and angiogenesis [23,298]. Mitochondrial fusion proteins, namely Mfn1, Mfn2, and Opa1, have been found to have a positive association with angiogenesis.…”