Metabolic and Immune Crosstalk in Cardiovascular Disease

Cardiovascular diseases including atherosclerosis and heart failure, arise from the intricate interplay of metabolic, immune, and neural dysregulation within vascular and cardiac tissues: This review focuses on integrating recent advances in metabolic and immune crosstalk of the cardiac vasculature that affects cardiometabolic health and disease progression. Coronary and lymphatic endothelial cells regulate cardiac metabolism, and their dysfunction is linked to cardiovascular diseases. Lymphatics maintain tissue homeostasis, including clearing metabolic waste, lipids, and immune cells, and their maladaptation in metabolic diseases worsens outcomes. Altered vascular endothelial metabolism in heart failure drives immune-mediated inflammation, fibrosis, and adverse cardiac remodeling. Concurrently, artery tertiary lymphoid organs formed in the adventitia of advanced atherosclerotic arteries, serve as pivotal neuroimmune hubs, coordinating local immunity through T and B cell activation and neurovascular signaling via artery-brain circuits. T cells within plaques and artery tertiary lymphoid organs undergo clonal expansion as a result of peripheral tolerance breakdown, with proinflammatory CD4⁺ and CD8⁺ subsets amplifying atherosclerosis, effects further shaped by systemic immune activation. Therapeutic strategies targeting endothelial cell metabolism, lymphatic dysfunction, neuroimmune crosstalk, and T cell plasticity hold promise for integrated cardiovascular disease management.