The Nexus of Redox Signaling, Metabolism, and Mitochondrial Function in Cardiovascular Diseases

Dear Colleagues,

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide, encompassing a diverse spectrum of disorders including atherosclerosis, coronary artery disease, myocardial infarction, heart failure, cardiomyopathies, hypertension, and cardiac arrhythmias. Despite significant advances in lipid-lowering therapies, antihypertensive agents, antithrombotic medications, and interventional procedures, CVD continues to impose an enormous global health and economic burden. Over the past decade, mounting evidence has established mitochondria as central regulators of cardiovascular health and disease, extending far beyond their classical role as cellular powerhouses. Mitochondria are now recognized as dynamic signaling organelles that integrate metabolic cues, redox homeostasis, calcium signaling, inflammation, and cell fate decisions. Dysregulation of these interconnected processes contributes to endothelial dysfunction, chronic inflammation, maladaptive cardiac remodeling, vascular stiffening, fibrosis, and ultimately heart failure. A hallmark of these pathological changes is mitochondrial reprogramming, characterized by enhanced aerobic glycolysis, impaired oxidative phosphorylation, excessive reactive oxygen species (ROS) generation, disrupted mitochondrial quality control, and altered mitochondrial dynamics—including imbalances in fission, fusion, biogenesis, and mitophagy.

Metabolic remodeling has emerged as a fundamental feature across virtually all forms of CVD. Similar to rapidly proliferating cancer cells, vascular endothelial cells, vascular smooth muscle cells, fibroblasts, and even stressed cardiomyocytes undergo a metabolic shift toward aerobic glycolysis—a phenomenon analogous to the Warburg effect. Collectively, three tightly interconnected processes have emerged as a unifying paradigm underlying cardiovascular pathogenesis: (1) metabolic reprogramming, (2) aberrant redox signaling, and (3) mitochondrial dynamics and quality control. Rather than acting independently, these pathways form an integrated regulatory network that governs cellular adaptation to stress and ultimately determines cardiovascular outcomes. Understanding the molecular mechanisms linking these processes has opened exciting opportunities for therapeutic intervention.

This Special Issue, "The Nexus of Redox Signaling, Metabolism, and Mitochondrial Function in Cardiovascular Diseases", seeks to provide a comprehensive platform for publishing basic, translational, and clinical research that elucidates how mitochondrial dysfunction orchestrates CVD progression. We invite original research articles and comprehensive reviews that investigate the molecular interplay among redox signaling, cellular metabolism, mitochondrial biology, and cardiovascular pathology.

Topics of interest include, but are not limited to:

• mitochondrial metabolism and metabolic reprogramming in vascular and cardiac cells;
• redox signaling, oxidative stress, and mitochondrial ROS in cardiac and vascular remodeling;
• mitochondrial dynamics, mitophagy, biogenesis, and quality control mechanisms;
• mitochondrial biomarkers for diagnosis, prognosis, and precision medicine;
• emerging mitochondrial therapeutic targets and translational strategies for CVDs;
• interactions between metabolism, redox homeostasis, and tissue remodeling;
• clinical correlates of mitochondrial dysfunction (e.g., biomarker discovery, multi‑omics approaches, hemodynamic–metabolic associations, and response to therapy).

By bringing together discoveries from molecular biology, metabolism, redox signaling, systems biology, and clinical cardiovascular research, this Special Issue aims to advance our understanding of mitochondrial mechanisms driving CVD and accelerate the translation of these insights into innovative diagnostic tools and therapeutic interventions that improve patient outcomes.

Dr. Manivannan Yegambaram
Dr. Adel Nefzi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Publisher’s Notice

Following discussions between the Life Editorial Office and the Guest Editor team, the Special Issue description has been revised. This change has been approved by the Life Editorial Board, and the Special Issue website has been updated accordingly on 6 August 2026. The Special Issue will continue to be handled by the Guest Editor team in accordance with MDPI’s Special Issue and editorial policies.

• cardiovascular diseases
• mitochondrial metabolism
• redox signaling
• oxidative stress
• HIF-1α regulation
• mitochondrial dynamics