Anti-fibrotic potential of AT₂ receptor agonists

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 (AT₂ R) is a novel anti-fibrotic strategy and we have reviewed the published in vivo preclinical data relating to the effects of compound 21 (C21), which is the only nonpeptide AT₂ R agonist that is currently available for use in chronic preclinical studies. In particular, the differential influence of AT₂ R on extracellular matrix status in various preclinical fibrotic models is discussed. Collectively, these studies demonstrate that pharmacological AT₂ R stimulation using C21 decreases organ fibrosis, which has been most studied in the setting of cardiovascular and renal disease. In addition, AT₂ R-mediated anti-inflammatory effects may contribute to the beneficial AT₂ R-mediated anti-fibrotic effects seen in preclinical models.