Mitochondrial Dysfunction and Therapeutic Perspectives in Cardiovascular Diseases

• Published in: International journal of molecular sciences Vol. 23; no. 24; p. 16053
• Main Authors: Liu, Yu, Huang, Yuejia, Xu, Chong, An, Peng, Luo, Yongting, Jiao, Lei, Luo, Junjie, Li, Yongzhi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16-12-2022; MDPI
• Subjects: Aortic aneurysms; Aortic dissection; Atherosclerosis; Autophagy; Cardiomyocytes; Cardiomyopathy; cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - genetics; Cardiovascular Diseases - metabolism; Cardiovascular Diseases - therapy; Coenzyme Q10; DNA, Mitochondrial - metabolism; Drug delivery; Electron Transport; Electron transport chain; Energy; Gene expression; Genomes; Genotype & phenotype; Heart failure; Homeostasis; Humans; Kinases; Metabolism; Mitochondria; Mitochondria - metabolism; Mitochondrial Diseases - drug therapy; Mitochondrial Diseases - therapy; Mitochondrial DNA; mitochondrial DNA mutation; mitochondrial dysfunction; mitophagy; Mutation; Nicotinamide; Oxidative phosphorylation; Oxidative stress; Pathogenesis; Phosphorylation; reactive oxygen species; Reactive Oxygen Species - metabolism; Respiration; Review; cardiovascular disease; mitophagy; therapeutic strategy; reactive oxygen species; mitochondrial DNA mutation; mitochondrial dysfunction; oxidative phosphorylation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232416053

High mortality rates due to cardiovascular diseases (CVDs) have attracted worldwide attention. It has been reported that mitochondrial dysfunction is one of the most important mechanisms affecting the pathogenesis of CVDs. Mitochondrial DNA (mtDNA) mutations may result in impaired oxidative phosphorylation (OXPHOS), abnormal respiratory chains, and ATP production. In dysfunctional mitochondria, the electron transport chain (ETC) is uncoupled and the energy supply is reduced, while reactive oxygen species (ROS) production is increased. Here, we discussed and analyzed the relationship between mtDNA mutations, impaired mitophagy, decreased OXPHOS, elevated ROS, and CVDs from the perspective of mitochondrial dysfunction. Furthermore, we explored current potential therapeutic strategies for CVDs by eliminating mtDNA mutations (e.g., mtDNA editing and mitochondrial replacement), enhancing mitophagy, improving OXPHOS capacity (e.g., supplement with NAD
, nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and nano-drug delivery), and reducing ROS (e.g., supplement with Coenzyme Q10 and other antioxidants), and dissected their respective advantages and limitations. In fact, some therapeutic strategies are still a long way from achieving safe and effective clinical treatment. Although establishing effective and safe therapeutic strategies for CVDs remains challenging, starting from a mitochondrial perspective holds bright prospects.