The dual role of angiotensin ii: From cardiovascular repair to tumor progression

Objective Angiotensin II (Ang II), the principal effector of the renin–angiotensin system, exhibits context-dependent dual roles in cardiovascular and oncological pathophysiology. This review systematically examines the molecular mechanisms underlying its contrasting functions in tissue repair and tumor progression while exploring the clinical translational implications of this functional plasticity. Methods Evidence on Ang II generation pathways, receptor subtype signaling, and downstream molecular networks was synthesized. The analysis focused on how receptor balance, microenvironmental cues, and signaling pathway crosstalk determine biological outcomes. Results In cardiovascular injury, transient low-concentration Ang II preferentially activates the protective AT2R and ACE2/Ang-(1–7)/Mas axes, promoting angiogenesis and anti-inflammatory repair. Conversely, in tumors, chronic hypoxia sustains AT1R activation, triggering Mitogen-activated protein kinase / Extracellular signal-regulated kinase (MAPK/ERK), phosphatidylinositol 3-kinase/protein kinase B(PI3 K/AKT), and Hypoxia-inducible factor / Vascular endothelial growth factor (HIF-VEGF) signaling that drive proliferation, EMT, immunosuppression, and therapy resistance. This functional shift depends on receptor subtype ratio, tissue microenvironment characteristics, and signaling node crosstalk. Conclusion Ang II acts as a bifunctional modulator rather than a detrimental factor, with its net effects determined by dynamic regulatory networks. Targeting this duality through receptor-specific strategies, combination immunotherapies, and stage-adaptive interventions may support precision therapeutic approaches for cardiovascular diseases, oncology, and cardio-oncology comorbidities.