Mitochondrial-Epigenetic Crosstalk in Cardiovascular Disease: From Mechanistic Insights to Precision Therapies

Cardiovascular diseases (CVDs) remain the foremost cause of morbidity and mortality worldwide, resulting from intricate interactions among genetic, metabolic, epigenetic, and environmental influences. Recent research underscores the pivotal role of mitochondria, not only in bioenergetics but also as key modulators of the epigenome through the production of metabolites, such as NAD⁺, acetyl-CoA, α-ketoglutarate, and succinate, that govern chromatin dynamics and gene transcription.

Advancements in cardiovascular biology have called attention to the need for an integrated understanding of how mitochondrial and epigenetic regulatory mechanisms converge in both the development and progression of CVDs. This is particularly pressing in light of growing evidence that highlights the bidirectional nature of mitochondria-epigenetic crosstalk: mitochondrial dysfunction can alter epigenetic marks (including DNA methylation, histone modifications, and non-coding RNAs), while, conversely, epigenetic modifications can modulate mitochondrial biogenesis, mitophagy, and immunometabolic signaling within cardiovascular tissues.

This Research Topic aims to advance clinical and molecular insights into the interplay between mitochondrial function and epigenetic regulation in CVD. Given the global disease burden and multifactorial nature of CVDs, clarifying these mechanisms promises to unlock new avenues for prediction, prevention, and therapy, especially as high-resolution multi-omics and AI-powered analytics reshape the research landscape.

We invite submissions that comprehensively address the epidemiological, molecular, and computational aspects of mitochondria-epigenetic regulation in the context of cardiovascular health and disease. We are particularly interested in studies that:

• Investigate the role of mitochondrial metabolites as epigenetic cofactors in CVD pathogenesis.
• Apply single-cell and spatial multi-omics to dissect mitochondrial-epigenetic interactions within cardiac tissues and disease models.
• Assess CRISPR-based and epigenome-editing approaches targeting mitochondrial pathways in preclinical or clinical cardiovascular models.
• Explore gut microbiome-derived metabolites that modulate mitochondrial-epigenetic signaling in the heart and its vasculature.
• Integrate AI-driven bioinformatics and automated pipelines for multi-layered data analysis and network modeling of mitochondrial-epigenetic interactions, facilitating hypothesis generation and reducing manual analysis workload.
• Evaluate immune-metabolic-epigenetic mechanisms underlying cardiovascular inflammation, fibrosis, and tissue remodeling.
• Elucidate sex- and age-specific mitochondrial-epigenetic signatures associated with CVDs, including atherosclerosis, heart failure with preserved ejection fraction (HFpEF), and metabolic cardiomyopathies.
• Characterize the gut-heart-mitochondria axis and its contribution to cardiovascular disease risk and progression.

Submissions should ideally leverage data from human clinical or cohort studies, translational animal models, or advanced in vitro systems, utilizing high-throughput, scalable, and reproducible methodologies. Studies that bridge basic mechanistic insights with clinical endpoints or new predictive models for CVD risk and progression are particularly welcome.

We accept original research articles, systematic reviews, meta-analyses, and brief reports that significantly advance knowledge at the intersection of mitochondria, epigenetics, and cardiovascular disease.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Classification
• Clinical Trial
• Community Case Study
• Curriculum, Instruction, and Pedagogy
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Classification
• Clinical Trial
• Community Case Study
• Curriculum, Instruction, and Pedagogy
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy and Practice Reviews
• Policy Brief
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: Mitochondrial dysfunction, epigenetic regulation, cardiovascular diseases, mitochondrial metabolites, chromatin state, gut-heart-mitochondria axis, single-cell multi-omics, CRISPR-based epigenome editing

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.