IL-17 as a therapeutic target in cardiovascular diseases: Mechanistic insights and translational opportunities

Interleukin-17 (IL-17), a pleiotropic cytokine produced by Th17 cells and innate immune cells, plays a pivotal role in cardiovascular diseases (CVDs) by bridging innate and adaptive immunity. Preclinical studies highlight its pro-inflammatory effects in atherosclerosis, myocardial infarction, hypertension, myocarditis, and heart failure, driving endothelial dysfunction, immune cell infiltration, oxidative stress, and tissue remodeling. Elevated IL-17 levels correlate with vulnerable plaque burden, adverse cardiac events, hypertension severity, and arrhythmogenesis. Paradoxically, IL-17 may stabilize plaques in specific contexts, underscoring its dual roles. Clinical data link IL-17 isoforms (e.g., IL-17A, IL-17E) to coronary artery disease progression and psychological comorbidities. While IL-17-targeted therapies (e.g., monoclonal antibodies) show promise in preclinical models, clinical outcomes remain heterogeneous, with controversies regarding cardiac adverse events (e.g.,coronary artery disease, pericarditis and atrial fibrillation) in autoimmune populations. Mechanistic insights emphasize IL-17's interactions with lipid metabolism, thrombotic pathways, and immune cross-talk. However, conflicting evidence on its protective versus detrimental effects necessitates further translational research. This review underscores the need for rigorous clinical trials to validate IL-17 modulation strategies in CVDs, balancing therapeutic benefits against potential adverse effects.