VEGF-A signalling at the vascular-immune interface: impact of anti-angiogenic agents on cardiovascular homeostasis and anthracycline-induced injury

Background Vascular endothelial growth factor A (VEGF-A) signalling is a central regulator of cardiovascular homeostasis, integrating endothelial function, cardiomyocyte survival, and immune cell trafficking. While thera- pies targeting VEGF-A and its receptors (VEGFRs) have transformed cancer treatment, their interference with physiological vascular signalling contributes to the observed cardiovascular toxicity, particularly when combined with anthracyclines. Emerging evidence indicates that anthracycline-mediated cardiotoxicity extends beyond direct myocardial injury to involve a coordinated activation of innate and adaptive immune pathways. Damage- associated molecular patterns (DAMPs) released by injured cardiomyocytes trigger inflammasome activation, cytokine production, and recruitment of neutrophils, macrophages, and T cells, establishing a sustained inflam- matory milieu.