Cardiovascular disease remains the leading global cause of death, and a major part of its residual risk is now understood to be inflammatory rather than purely lipid-driven. Immunometabolism provides the missing link between metabolic stress and immune activation: excess lipids, hyperglycemia, and tissue hypoxia reprogram immune and vascular cells toward glycolysis, altered glutamine use, mitochondrial dysfunction, and durable epigenetic memory. In atherosclerosis, this metabolic shift fuels endothelial dysfunction, macrophage foam-cell formation, cytokine release, defective efferocytosis, and plaque instability. The concept extends beyond the plaque itself through trained immunity, in which monocytes and bone marrow progenitors retain a pro-inflammatory memory that can persist after the original trigger has passed. This helps explain why myocardial infarction, diabetes, and hyperlipidemia can leave a long inflammatory imprint on the vasculature. Immunometabolism also contributes to thromboinflammation, where activated platelets, neutrophils, and extracellular traps reinforce clot formation and amplify arterial injury. In heart failure, postischemic remodeling and chronic congestion are accompanied by immune-cell and cardiomyocyte metabolic remodeling that sustains inflammation, fibrosis, and adverse ventricular remodeling. Clinical trials targeting inflammation, especially canakinumab and low-dose colchicine, have shown that suppressing inflammatory pathways can reduce cardiovascular events, supporting the translational value of this biology. A clearer understanding of immunometabolic circuits may enable better risk stratification, biomarker-guided therapy, and new treatments that simultaneously stabilize plaques, reduce thrombosis, and improve postinfarction healing.
Rani et al. (Sat,) studied this question.