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 (AT₂R) 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 AT₂R agonist that is currently available for use in chronic preclinical studies. In particular, the differential influence of AT₂R on extracellular matrix status in various preclinical fibrotic models is discussed. Collectively, these studies demonstrate that pharmacological AT₂R stimulation using C21 decreases organ fibrosis, which has been most studied in the setting of cardiovascular and renal disease. In addition, AT₂R-mediated anti-inflammatory effects may contribute to the beneficial AT₂R-mediated anti-fibrotic effects seen in preclinical models.