AUTHOR=Wang Yan , Del Borgo Mark , Lee Huey W. , Baraldi Dhaniel , Hirmiz Baydaa , Gaspari Tracey A. , Denton Kate M. , Aguilar Marie-Isabel , Samuel Chrishan S. , Widdop Robert E. 

TITLE=Anti-fibrotic Potential of AT2 Receptor Agonists

JOURNAL=Frontiers in Pharmacology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2017.00564

DOI=10.3389/fphar.2017.00564

ISSN=1663-9812

ABSTRACT=<p>There are a number of therapeutic targets to treat organ fibrosis that are under investigation in preclinical models. There is increasing evidence that stimulation of the angiotensin II type 2 receptor (AT<sub>2</sub>R) is a novel anti-fibrotic strategy and we have reviewed the published <italic>in vivo</italic> preclinical data relating to the effects of compound 21 (C21), which is the only nonpeptide AT<sub>2</sub>R agonist that is currently available for use in chronic preclinical studies. In particular, the differential influence of AT<sub>2</sub>R on extracellular matrix status in various preclinical fibrotic models is discussed. Collectively, these studies demonstrate that pharmacological AT<sub>2</sub>R stimulation using C21 decreases organ fibrosis, which has been most studied in the setting of cardiovascular and renal disease. In addition, AT<sub>2</sub>R-mediated anti-inflammatory effects may contribute to the beneficial AT<sub>2</sub>R-mediated anti-fibrotic effects seen in preclinical models.</p>