Rodriguez-Gonzalez, MoisesLubian-Gutierrez, ManuelCascales-Poyatos, Helena MariaPerez-Reviriego, Alvaro AntonioCastellano-Martinez, Ana2022-10-262022-10-262020-12-31Rodriguez-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):3561661-6596http://hdl.handle.net/10668/4289Dystrophin-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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/DystrohinopathyDuchenne muscular diseaseBecker muscular diseaseDystrophic deficient cardiomyopathyCardiac fibrosisRenin angiotensin systemAngiotensin 2Angiotensin converter enzyme inhibitorsAngiotensin receptor blockersEnfermedades muscularesDistrofia muscular de DuchenneCardiomiopatíasDistrofias muscularesFibrosisSistema renina-angiotensinaAngiotensina IIInhibidores de la enzima convertidora de angiotensinaAntagonistas de receptores de angiotensinaMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Diseases::Cardiovascular Diseases::Heart Diseases::CardiomyopathiesMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Contractile Proteins::Muscle Proteins::DystrophinMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Renin-Angiotensin SystemMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Angiotensin Receptor AntagonistsMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protease Inhibitors::Angiotensin-Converting Enzyme InhibitorsMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormone Antagonists::Mineralocorticoid Receptor AntagonistsMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Angiotensins::Angiotensin IIMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Dystrophinreview article33396334open access10.3390/ijms220103561422-0067PMC7796305