Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Role of the Renin-Angiotensin-Aldosterone System in Dystrophin-Deficient Cardiomyopathy

Version 1 : Received: 16 December 2020 / Approved: 18 December 2020 / Online: 18 December 2020 (07:18:16 CET)

A peer-reviewed article of this Preprint also exists.

Rodriguez-Gonzalez, M.; Lubian-Gutierrez, M.; Cascales-Poyatos, H.M.; Perez-Reviriego, A.A.; Castellano-Martinez, A. Role of the Renin–Angiotensin–Aldosterone System in Dystrophin-Deficient Cardiomyopathy. Int. J. Mol. Sci. 2021, 22, 356. Rodriguez-Gonzalez, M.; Lubian-Gutierrez, M.; Cascales-Poyatos, H.M.; Perez-Reviriego, A.A.; Castellano-Martinez, A. Role of the Renin–Angiotensin–Aldosterone System in Dystrophin-Deficient Cardiomyopathy. Int. J. Mol. Sci. 2021, 22, 356.

Journal reference: Int. J. Mol. Sci. 2020, 22, 356
DOI: 10.3390/ijms22010356

Abstract

Dystrophin-deficient cardiomyopathy (DDC) is currently the leading cause of death in patients with dystrophinopathies. Targeting myocardial fibrosis (MF) has become a major therapeutic goal in order to prevent the occurrence of DDC. We aimed to review and summarize the current evidence about the role of the renin-angiotensin-aldosterone system (RAAS) in the development and perpetuation of MF in DCC. We conducted a comprehensive search of peer-reviewed English literature on PubMed about this subject. We found increasing preclinical evidence from studies in animal models during the last 20 years pointing out a central role of RAAS in the development of MF in DDC. Local tissue RAAS acts directly mainly through its main fibrotic component angiotensin II (ANG2) and its transducer receptor (AT1R) and downstream TGF-b pathway. Also, it modulates the actions of most of the remaining pro-fibrotic factors involved in DDC. Despite limited clinical evidence, RAAS blockade constitutes the most studied, available and promising therapeutic strategy against MF and DDC. Conclusion: Based on the evidence reviewed, it would be recommendable to start RAAS blockade therapy through angiotensin converter enzyme inhibitors (ACEI) or AT1R blockers (ARBs) alone or in combination with mineralocorticoid receptor antagonists (MRa) at the youngest age after the diagnosis of dystrophinopathies, in order to delay the occurrence or slow the progression of MF, even before the detection of any cardiovascular alteration.

Subject Areas

dystrohinopathy; Duchenne muscular disease; Becker muscular disease; dystrophic deficient cardiomyopathy; cardiac fibrosis; renin angiotensin system; angiotensin 2; angiotensin converter enzyme inhibitors; angiotensin receptor blockers; heart failure

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.