Immunometabolism in Cardiac Remodeling: Mechanisms and Therapeutic Perspectives

Cardiovascular diseases remain the leading cause of mortality worldwide, and one of the key mechanisms driving the development of heart failure is pathological remodeling of the myocardium. This process involves complex structural, cellular, and metabolic alterations in which the immune system and its interactions with cardiomyocytes and fibroblasts play a central role. The aim of this work was to present the current state of knowledge on immunometabolism in cardiac remodeling and to discuss its pathophysiological relevance and therapeutic potential. This review focuses on the metabolism of cardiac macrophages, highlighting the differences between the pro-inflammatory (M1) and reparative (M2) phenotypes and their impact on inflammation, fibrosis, and myocardial regeneration. The roles of major metabolic pathways, including glycolysis, oxidative phosphorylation, fatty acid oxidation, and glutaminolysis, are discussed, as well as the importance of the NLRP3 inflammasome and efferocytosis in regulating the inflammatory response. Furthermore, the review briefly incorporates recent insights into neutrophil, T cell, and regulatory T cell (Treg) metabolism and their contributions to inflammation, repair, and fibrotic remodeling. Particular attention is also given to cardiac fibroblasts and their metabolic reprogramming during fibrosis, with emphasis on the pivotal role of transforming growth factor-β (TGF-β) signaling. The review further discusses the role of microRNAs as mediators of intercellular communication integrating immunological and metabolic signals. The work is complemented by a discussion of therapeutic perspectives, including modulation of macrophage metabolism, fibrogenic signaling pathways, mitochondrial function, and miRNA-based therapies. Immunometabolism emerges as a promising research field whose further exploration may contribute to the development of novel, more precise strategies for the treatment of cardiovascular diseases.