Angiotensin AT2 receptors reduce inflammation and fibrosis in cardiovascular remodeling.

Elena Kaschina, Dilyara Lauer, Christoph Lange, Thomas Unger

Biochemical pharmacology 2024 Apr

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The angiotensin AT2 receptor (AT2R), 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 AT2R activates complex signalling pathways linked to cellular proliferation, differentiation, anti-inflammation, antifibrosis, and induction or inhibition of apoptosis. The anti-inflammatory effect of AT2R activation is commonly associated with reduced fibrosis in different models. Current discoveries demonstrated a direct impact of AT2Rs 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 AT2R in regard to immunity, inflammation and fibrosis in the heart and blood vessels. In particular, the differential influence of the AT2R on cardiovascular remodeling in preclinical models of myocardial infarction, heart failure and aneurysm formation are discussed. Overall, these studies demonstrate that AT2R stimulation represents a promising therapeutic approach to counteract myocardial and aortic damage in cardiovascular diseases. Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Elena Kaschina, Dilyara Lauer, Christoph Lange, Thomas Unger. Angiotensin AT2 receptors reduce inflammation and fibrosis in cardiovascular remodeling. Biochemical pharmacology. 2024 Apr;222:116062