Cardiometabolic effects of sacubitril/valsartan in a rat model of heart failure with preserved ejection fraction.

Autor: Moraña-Fernández S; Cellular and Molecular Cardiology Research Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Área Sanitaria Santiago de Compostela e Barbanza (SERGAS), Santiago de Compostela, Spain; Cardiology Group, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain., Vázquez-Abuín X; Cellular and Molecular Cardiology Research Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Área Sanitaria Santiago de Compostela e Barbanza (SERGAS), Santiago de Compostela, Spain; Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Aragón-Herrera A; Cellular and Molecular Cardiology Research Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Área Sanitaria Santiago de Compostela e Barbanza (SERGAS), Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain. Electronic address: alana.aragon.herrera@sergas.es., Anido-Varela L; Cellular and Molecular Cardiology Research Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Área Sanitaria Santiago de Compostela e Barbanza (SERGAS), Santiago de Compostela, Spain; Universidade de Santiago de Compostela, Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain., García-Seara J; Cellular and Molecular Cardiology Research Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Área Sanitaria Santiago de Compostela e Barbanza (SERGAS), Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain; Arrhytmia Unit, Cardiology Department, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Área Sanitaria Santiago de Compostela e Barbanza (SERGAS), Santiago de Compostela, Spain; Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS, Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Otero-García Ó; Cellular and Molecular Cardiology Research Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Área Sanitaria Santiago de Compostela e Barbanza (SERGAS), Santiago de Compostela, Spain; Cardiology Department, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Área Sanitaria Santiago de Compostela e Barbanza (SERGAS), Santiago de Compostela, Spain., Rodríguez-Penas D; Cellular and Molecular Cardiology Research Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Área Sanitaria Santiago de Compostela e Barbanza (SERGAS), Santiago de Compostela, Spain; Cardiology Department Clinical Trial Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Área Sanitaria Santiago de Compostela e Barbanza (SERGAS), Santiago de Compostela, Spain., Campos-Toimil M; Physiology and Pharmacology of Chronic Diseases (FIFAEC), Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Otero-Santiago M; Cellular and Molecular Cardiology Research Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Área Sanitaria Santiago de Compostela e Barbanza (SERGAS), Santiago de Compostela, Spain; Clinical Biochemistry Laboratory, Área Sanitaria Santiago de Compostela e Barbanza (SERGAS), Santiago de Compostela, Spain., Rodrigues A; Cardiovascular R&D Centre - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal., Gonçalves A; Cardiovascular R&D Centre - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal., Pereira Morais J; CINTESIS@RISE, NOVA Medical School|Faculdade de Ciências Médicas, NMS|FCM, Universidade Nova de Lisboa, UnIC@RISE - Cardiovascular Research Centre, Faculdade de Medicina, Universidade do Porto, Porto, Portugal., Alves IN; Cardiovascular R&D Centre - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal., Sousa-Mendes C; Cardiovascular R&D Centre - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal., Falcão-Pires I; Cardiovascular R&D Centre - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal., González-Juanatey JR; Cellular and Molecular Cardiology Research Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Área Sanitaria Santiago de Compostela e Barbanza (SERGAS), Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain; Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS, Universidade de Santiago de Compostela, Santiago de Compostela, Spain; Cardiology Department, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Área Sanitaria Santiago de Compostela e Barbanza (SERGAS), Santiago de Compostela, Spain., Feijóo-Bandín S; Cellular and Molecular Cardiology Research Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Área Sanitaria Santiago de Compostela e Barbanza (SERGAS), Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain., Lago F; Cellular and Molecular Cardiology Research Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Área Sanitaria Santiago de Compostela e Barbanza (SERGAS), Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain.
Jazyk: angličtina
Zdroj: Biochemical pharmacology [Biochem Pharmacol] 2024 Dec; Vol. 230 (Pt 1), pp. 116571. Date of Electronic Publication: 2024 Oct 16.
DOI: 10.1016/j.bcp.2024.116571
Abstrakt: The promising results obtained in the PARADIGM-HF trial prompted the approval of sacubitril/valsartan (SAC/VAL) as a first-in-class treatment for heart failure with reduced ejection fraction (HFrEF) patients. The effect of SAC/VAL treatment was also studied in patients with heart failure with preserved ejection fraction (HFpEF) and, although improvements in New York Heart Association (NYHA) class, HF hospitalizations, and cardiovascular deaths were observed, these results were not so promising. However, the demand for HFpEF therapies led to the approval of SAC/VAL as an alternative treatment, although further studies are needed. We aimed to elucidate the effects of a 9-week SAC/VAL treatment in cardiac function and metabolism using a preclinical model of HFpEF, the Zucker Fatty and Spontaneously Hypertensive (ZSF1) rats. We found that SAC/VAL significantly improved diastolic function parameters and modulated respiratory quotient during exercise. Ex-vivo studies showed that SAC/VAL treatment significantly decreased heart, liver, spleen, and visceral fat weights; cardiac hypertrophy and percentage of fibrosis; lipid infiltration in liver and circulating levels of cholesterol and sodium. Moreover, SAC/VAL reduced glycerophospholipids, cholesterol, and cholesteryl esters while increasing triglyceride levels in cardiac tissue. In conclusion, SAC/VAL treatment improved diastolic and hepatic function, respiratory metabolism, reduced hypercholesterolemia and cardiac fibrosis and hypertrophy, and was able to modulate cardiac metabolic profile. Our findings might provide further insight into the therapeutic benefits of SAC/VAL treatment in obese patients with HFpEF.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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