Targeting Metabolic Drivers of Cardiovascular Disease: Insights for Therapeutic Innovation.
- 1Department of Molecular, Cellular and Biomedical Sciences, City University of New York - School of Medicine, New York City, NY, 10031, USA.
- 2Department of Medicine and Health Sciences, University of Molise, Campobasso, 86100, Italy.
- 3Casa di Cura "Clinica Montevergine", Mercogliano (Avellino), 83013, Italy.
Abstract
Cardiovascular disease (CVD) remains the leading cause of death worldwide, and metabolic dysfunction is increasingly recognized as an important component of its pathophysiology. Clinical evidence supports a role for dysregulated lipid and glucose metabolism in atherosclerosis, heart failure, and cardiometabolic disease, while alterations in amino acid metabolism, mitochondrial energetics, redox signaling, and immunometabolic pathways are supported by growing experimental and observational evidence. Advances in metabolomics, systems biology, and multi-omics approaches have further identified metabolic signatures associated with cardiovascular phenotypes and have provided new insights into pathways regulating endothelial function, vascular inflammation, oxidative stress, and cardiac remodeling. This review synthesizes established clinical evidence and emerging experimental findings on metabolic mechanisms in CVD, with particular emphasis on their potential therapeutic and biomarker implications. We discuss current and investigational strategies targeting lipid and glucose metabolism, mitochondrial dysfunction, oxidative stress, and immunometabolic signaling, while distinguishing clinically validated approaches from those that remain primarily preclinical or hypothesis-generating. Key translational challenges include the complexity and tissue specificity of metabolic networks, limitations of existing experimental models, potential safety liabilities, and the need for longitudinal studies integrating metabolic and clinical phenotypes. Finally, we examine how metabolomics, AI, organ-on-chip models, and systems-level approaches could improve target identification, patient stratification, and therapeutic development. These advances provide a framework for translating mechanistic insights into metabolism-informed cardiovascular therapies and biomarkers, while highlighting the evidence gaps that must be addressed before broader clinical implementation.
Related
- Natural Products and Their Derivatives in Cancer, Cardiovascular disease, and COVID-19: Mechanistic Insights, Formulation Strategies, and Therapeutic Potential
- Natural Bioactive Compounds Targeting Gut Barrier Integrity and Metabolic Endotoxemia in Cardiometabolic Disease: Mechanistic Insights and Translational Perspectives
- Emerging Therapeutic Strategies for Targeting Hyaluronan in Metabolic Disease from Molecular Design to Clinical Translation
- Engineering extracellular vesicles for inflammatory bowel disease and colitis-associated colorectal cancer: from therapeutic innovation to clinical translation
- Enzyme-Immobilized Nanomaterials for Endocrine Disorders: Therapeutic Innovation and Translational Challenges.
BibTeX
@article{kansakar2026targeting,
title = {{Targeting Metabolic Drivers of Cardiovascular Disease: Insights for Therapeutic Innovation.}},
author = {Urna Kansakar and Malik Hyman and Enrico Volpe and Pasquale Mone and Yifei Qin and Gaetano Santulli},
journal = {Drug design, development and therapy},
year = {2026},
month = oct,
doi = {10.2147/dddt.s611903},
url = {https://europepmc.org/article/MED/42928775},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Targeting Metabolic Drivers of Cardiovascular Disease: Insights for Therapeutic Innovation.
AU - Urna Kansakar
AU - Malik Hyman
AU - Enrico Volpe
AU - Pasquale Mone
AU - Yifei Qin
AU - Gaetano Santulli
PY - 2026
DA - 2026/10/21
JO - Drug design, development and therapy
DO - 10.2147/dddt.s611903
UR - https://europepmc.org/article/MED/42928775
AB - Cardiovascular disease (CVD) remains the leading cause of death worldwide, and metabolic dysfunction is increasingly recognized as an important component of its pathophysiology. Clinical evidence supports a role for dysregulated lipid and glucose metabolism in atherosclerosis, heart failure, and cardiometabolic disease, while alterations in amino acid metabolism, mitochondrial energetics, redox signaling, and immunometabolic pathways are supported by growing experimental and observational evidence. Advances in metabolomics, systems biology, and multi-omics approaches have further identified metabolic signatures associated with cardiovascular phenotypes and have provided new insights into pathways regulating endothelial function, vascular inflammation, oxidative stress, and cardiac remodeling. This review synthesizes established clinical evidence and emerging experimental findings on metabolic mechanisms in CVD, with particular emphasis on their potential therapeutic and biomarker implications. We discuss current and investigational strategies targeting lipid and glucose metabolism, mitochondrial dysfunction, oxidative stress, and immunometabolic signaling, while distinguishing clinically validated approaches from those that remain primarily preclinical or hypothesis-generating. Key translational challenges include the complexity and tissue specificity of metabolic networks, limitations of existing experimental models, potential safety liabilities, and the need for longitudinal studies integrating metabolic and clinical phenotypes. Finally, we examine how metabolomics, AI, organ-on-chip models, and systems-level approaches could improve target identification, patient stratification, and therapeutic development. These advances provide a framework for translating mechanistic insights into metabolism-informed cardiovascular therapies and biomarkers, while highlighting the evidence gaps that must be addressed before broader clinical implementation.
SN - 1177-8881
ER -