Angiotensin AT2 receptors reduce inflammation and fibrosis in cardiovascular remodeling

The angiotensin AT2 receptor (AT R), an important member of the "protective arm" of the renin-angiotensin system (RAS), has been recently defined as a therapeutic target in different pathological conditions. The AT R activates complex signalling pathways linked to cellular proliferation, differentiation, anti-inflammation, antifibrosis, and induction or inhibition of apoptosis. The anti-inflammatory effect of AT R activation is commonly associated with reduced fibrosis in different models. Current discoveries demonstrated a direct impact of AT Rs on the regulation of cytokines, transforming growth factor beta1 (TGF-beta1), matrix metalloproteases (MMPs), and synthesis of the extracellular matrix components. This review article summarizes current knowledge on the AT R in regard to immunity, inflammation and fibrosis in the heart and blood vessels. In particular, the differential influence of the AT R on cardiovascular remodeling in preclinical models of myocardial infarction, heart failure and aneurysm formation are discussed. Overall, these studies demonstrate that AT R stimulation represents a promising therapeutic approach to counteract myocardial and aortic damage in cardiovascular diseases.