Mitochondrial cardiovascular diseases: molecular mechanisms, multi-omics exploration and therapeutic strategies

Recent research highlights that abnormal mitochondrial function is a key feature in several cardiovascular diseases (CVDs), including aortic dissection, aortic aneurysm, atherosclerosis, pulmonary hypertension, and heart failure. We propose a novel concept termed mitochondrial cardiovascular diseases (Mito-CVDs) to define these conditions, which involve heart and vascular disorders directly driven by mitochondrial impairments, with the aim of highlighting the critical role of mitochondria in CVDs.

This review aims to explore the complex relationship between mitochondrial impairments and Mito-CVDs, offering insights into potential molecular mechanisms and therapeutic strategies to address these diseases.

The role of mitochondrial impairments in CVDs is expounded upon in detail, encompassing aspects such as excessive production of Reactive Oxygen Species (ROS), diminished Oxidative Phosphorylation (OXPHOS) capacity, and perturbations in Ca²⁺ transport. We also recapitulate the application of mitochondrial multi-omics, incorporating genomics, transcriptomics, proteomics, and metabolomics, within the realm of CVDs research. Additionally, single-cell mtDNA sequencing technology unfolds novel vistas for disclosing mitochondrial heterogeneity and status functional in Mito-CVDs. To enhance the understanding of Mito-CVDs, we present advanced diagnostic tools and categorize specific subtypes within each class of these disorders. Additionally, we propose Predictive, Preventive, and Personalized Medicine (PPPM) strategies designed to address mitochondrial impairments. Emerging therapeutic approaches are also discussed, including small-molecule modulators targeting key metabolic pathways, precision-based mtDNA editing technologies, and mitochondrial transplantation. A profound and exhaustive analysis of the mechanisms and therapeutic avenues associated with Mito-CVDs holds the potential to engender novel perspectives and opportunities for the prevention and treatment of CVDs.