Anti-fibrotic potential of AT2 receptor agonists

Research output: Contribution to journalArticleOtherpeer-review

Abstract

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.

Original languageEnglish
Article number564
Number of pages7
JournalFrontiers in Pharmacology
Volume8
DOIs
Publication statusPublished - 31 Aug 2017

Keywords

  • AT receptor
  • Cardiac fibrosis
  • Compound 21
  • Inflammation
  • Renal fibrosis

Cite this

@article{a9e40b06274d446f8d09c8cf5146a184,
title = "Anti-fibrotic potential of AT2 receptor agonists",
abstract = "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.",
keywords = "AT receptor, Cardiac fibrosis, Compound 21, Inflammation, Renal fibrosis",
author = "Yan Wang and {Del Borgo}, Mark and Lee, {Huey W.} and Dhaniel Baraldi and Baydaa Hirmiz and Gaspari, {Tracey A.} and Denton, {Kate M.} and Marie-Isabel Aguilar and Samuel, {Chrishan S.} and Widdop, {Robert E.}",
year = "2017",
month = "8",
day = "31",
doi = "10.3389/fphar.2017.00564",
language = "English",
volume = "8",
journal = "Frontiers in Pharmacology",
issn = "1663-9812",
publisher = "Frontiers Media",

}

Anti-fibrotic potential of AT2 receptor agonists. / 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.

In: Frontiers in Pharmacology, Vol. 8, 564, 31.08.2017.

Research output: Contribution to journalArticleOtherpeer-review

TY - JOUR

T1 - Anti-fibrotic potential of AT2 receptor agonists

AU - Wang, Yan

AU - Del Borgo, Mark

AU - Lee, Huey W.

AU - Baraldi, Dhaniel

AU - Hirmiz, Baydaa

AU - Gaspari, Tracey A.

AU - Denton, Kate M.

AU - Aguilar, Marie-Isabel

AU - Samuel, Chrishan S.

AU - Widdop, Robert E.

PY - 2017/8/31

Y1 - 2017/8/31

N2 - 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.

AB - 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.

KW - AT receptor

KW - Cardiac fibrosis

KW - Compound 21

KW - Inflammation

KW - Renal fibrosis

UR - http://www.scopus.com/inward/record.url?scp=85028471491&partnerID=8YFLogxK

U2 - 10.3389/fphar.2017.00564

DO - 10.3389/fphar.2017.00564

M3 - Article

VL - 8

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

SN - 1663-9812

M1 - 564

ER -