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Review
. 2024 May 14;9(9):2596-2607.
doi: 10.1016/j.ekir.2024.05.005. eCollection 2024 Sep.

The Role of Mitochondrial Dysfunction in CKD-Related Vascular Calcification: From Mechanisms to Therapeutics

Junmin Huang  1 , Junfeng Hao  1 , Peng Wang  1 , Yongzhi Xu  1
Affiliations
Review

The Role of Mitochondrial Dysfunction in CKD-Related Vascular Calcification: From Mechanisms to Therapeutics

Junmin Huang et al. Kidney Int Rep. .

Abstract

Vascular calcification (VC) is a common complication of chronic kidney disease (CKD) and is closely associated with cardiovascular events. The transdifferentiation of vascular smooth muscles (VSMCs) into an osteogenic phenotype is hypothesized to be the primary cause underlying VC. However, there is currently no effective clinical treatment for VC. Growing evidence suggests that mitochondrial dysfunction accelerates the osteogenic differentiation of VSMCs and VC via multiple mechanisms. Therefore, elucidating the relationship between the osteogenic differentiation of VSMCs and mitochondrial dysfunction may assist in improving VC-related adverse clinical outcomes in patients with CKD. This review aimed to summarize the role of mitochondrial biogenesis, mitochondrial dynamics, mitophagy, and metabolic reprogramming, as well as mitochondria-associated oxidative stress (OS) and senescence in VC in patients with CKD to offer valuable insights into the clinical treatment of VC.

Keywords: CKD; mitochondria; osteogenic transdifferentiation; vascular calcification; vascular smooth muscle cell.

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Figures

Figure 1
Figure 1
Mitochondrial biogenesis with PGC-1α as the regulatory center is highly involved in the osteogenic transdifferentiation of VSMCs through apoptosis, mitochondrial dynamics, cell autophagy, etc., (Created with BioRender.com). PGC-1α, peroxisome proliferator-activated receptor gamma coactivator-1α; VSMCs, vascular smooth muscles.
Figure 2
Figure 2
DRP1-driven mitochondrial division promotes the osteogenic transdifferentiation of VSMCs and is regulated by melatonin, lactic acid, etc., whereas mitochondrial fusion exerts a protective role against VC (Created with BioRender.com). DRP1, dynamin-related protein 1; VC, vascular calcification; VSMCs, vascular smooth muscles.
Figure 3
Figure 3
Mitophagy and mitochondrial biogenesis preserve mitochondrial mass and protect against cellular damage. Lactic acid exerts a strong promoting effect on the osteogenic differentiation of VSMCs by interfering with mitophagy, including both ubiquitin-dependent and non-ubiquitin-dependent pathways (Created with BioRender.com). VSMCs, vascular smooth muscles.
See this image and copyright information in PMC

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