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

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2020-12-31

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Rodriguez-Gonzalez, Moises
Lubian-Gutierrez, Manuel
Cascales-Poyatos, Helena Maria
Perez-Reviriego, Alvaro Antonio
Castellano-Martinez, Ana

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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. Additionally, 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.

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Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Diseases::Cardiovascular Diseases::Heart Diseases::Cardiomyopathies
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Contractile Proteins::Muscle Proteins::Dystrophin
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Renin-Angiotensin System
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Angiotensin Receptor Antagonists
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protease Inhibitors::Angiotensin-Converting Enzyme Inhibitors
Medical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormone Antagonists::Mineralocorticoid Receptor Antagonists
Medical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Angiotensins::Angiotensin II
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Dystrophin

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Dystrohinopathy, Duchenne muscular disease, Becker muscular disease, Dystrophic deficient cardiomyopathy, Cardiac fibrosis, Renin angiotensin system, Angiotensin 2, Angiotensin converter enzyme inhibitors, Angiotensin receptor blockers, Enfermedades musculares, Distrofia muscular de Duchenne, Cardiomiopatías, Distrofias musculares, Fibrosis, Sistema renina-angiotensina, Angiotensina II, Inhibidores de la enzima convertidora de angiotensina, Antagonistas de receptores de angiotensina

Citation

Rodriguez-Gonzalez M, Lubian-Gutierrez M, Cascales-Poyatos HM, Perez-Reviriego AA, Castellano-Martinez A. Role of the Renin-Angiotensin-Aldosterone System in Dystrophin-Deficient Cardiomyopathy. Int J Mol Sci. 2020 Dec 31;22(1):356