1. Calpains as Potential Therapeutic Targets for Myocardial Hypertrophy
- Author
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David Aluja, Sara Delgado-Tomás, Marisol Ruiz-Meana, José A. Barrabés, Javier Inserte, Institut Català de la Salut, [Aluja D, Delgado-Tomás S] Grup de Recerca en Malalties Cardiovasculars, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Ruiz-Meana M, Barrabés JA, Inserte J] Grup de Recerca en Malalties Cardiovasculars, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
Heart Failure ,Cardiovascular Diseases::Heart Diseases::Heart Failure [DISEASES] ,Calpain ,Organic Chemistry ,Calcium-Binding Proteins ,Enzims - Ús terapèutic ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Cardiomegaly ,General Medicine ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,enfermedades cardiovasculares::enfermedades cardíacas::insuficiencia cardíaca [ENFERMEDADES] ,Catalysis ,Computer Science Applications ,Inorganic Chemistry ,Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Cysteine Proteases::Cysteine Endopeptidases::Calpain [CHEMICALS AND DRUGS] ,enzimas y coenzimas::enzimas::hidrolasas::péptido hidrolasas::cisteína proteasas::cisteína endopeptidasas::calpaína [COMPUESTOS QUÍMICOS Y DROGAS] ,Animals ,Physical and Theoretical Chemistry ,Insuficiència renal aguda - Tractament ,Molecular Biology ,Spectroscopy - Abstract
Calpain; Calpastatin; Myocardial hypertrophy Calpaína; Calpastatina; Hipertrofia miocárdica Calpaïna; Calpastatina; Hipertròfia miocàrdica Despite advances in its treatment, heart failure remains a major cause of morbidity and mortality, evidencing an urgent need for novel mechanism-based targets and strategies. Myocardial hypertrophy, caused by a wide variety of chronic stress stimuli, represents an independent risk factor for the development of heart failure, and its prevention constitutes a clinical objective. Recent studies performed in preclinical animal models support the contribution of the Ca2+-dependent cysteine proteases calpains in regulating the hypertrophic process and highlight the feasibility of their long-term inhibition as a pharmacological strategy. In this review, we discuss the existing evidence implicating calpains in the development of cardiac hypertrophy, as well as the latest advances in unraveling the underlying mechanisms. Finally, we provide an updated overview of calpain inhibitors that have been explored in preclinical models of cardiac hypertrophy and the progress made in developing new compounds that may serve for testing the efficacy of calpain inhibition in the treatment of pathological cardiac hypertrophy. This study was funded by the Instituto de Salud Carlos III of the Spanish Ministry of Health FIS-PI20/01681) and the research network CIBERCV (CB16/11/00479).
- Published
- 2022