Roles of inflammation and metabolic dysfunction in cardiovascular diseases: molecular mechanisms and therapeutic targets.

Abstract

Cardiovascular disease progression is shaped by a close interaction between metabolic adaptation and inflammatory signaling. In injured cardiac and vascular tissues, ischemia, pressure overload, lipid stress and metabolic excess reshape how cardiomyocytes, endothelial cells, immune cells and fibroblasts sense damage and communicate with their microenvironment. Cardiovascular inflammation follows a staged tissue response, from danger-signal sensing and nuclear factor-κB-related priming to inflammasome activation, cytokine amplification, leukocyte recruitment, efferocytosis and chronic remodeling. Metabolic reprogramming shapes this sequence by altering substrate use, redox control, biosynthetic routing and metabolite signaling. A major challenge is that glycolysis, fatty acid oxidation and amino-acid metabolism do not carry fixed biological meanings; their effects depend on the cell type, measurement layer and disease phase in which they occur. This review examines metabolism-inflammation crosstalk in cardiovascular disease by linking core inflammatory pathways with metabolic sensors, immune-cell metabolic reprogramming and signaling metabolites, then comparing disease-specific mechanisms in myocardial infarction/ischemia-reperfusion injury, heart failure, atherosclerosis, hypertrophic remodeling and myocardial fibrosis. We emphasize how apparently similar metabolic shifts can represent adaptive repair, inflammatory amplification or maladaptive remodeling in different compartments. The therapeutic discussion separates pathway activity from targetability and uses anti-inflammatory trials and metabolic interventions to define when patient selection, pathway engagement and safety considerations support targeted treatment.