| Autor: |
Asensio Lopez MDC; Biomedical Research Institute Virgen de La Arrixaca (IMIB-Arrixaca), University of Murcia, Ctra. Madrid-Cartagena S/N, 30120, Murcia, Spain., Lax A; Biomedical Research Institute Virgen de La Arrixaca (IMIB-Arrixaca), University of Murcia, Ctra. Madrid-Cartagena S/N, 30120, Murcia, Spain. alax@um.es., Hernandez Vicente A; Cardiology Department, IMIB-Arrixaca, University of Murcia, Hospital Virgen de la Arrixaca, Murcia, Spain., Saura Guillen E; Endocrinology Department, Hospital Virgen de La Arrixaca, University of Murcia, Murcia, Spain., Hernandez-Martinez A; Endocrinology Department, Hospital Virgen de La Arrixaca, University of Murcia, Murcia, Spain., Fernandez Del Palacio MJ; Veterinary Medicine and Surgery Department, Veterinary Teaching Hospital, University of Murcia, Murcia, Spain., Bayes-Genis A; Heart Institute, Hospital Universitari German Trías i Puyol, CIBERCV, BadalonaMadrid, Spain., Pascual Figal DA; Cardiology Department, IMIB-Arrixaca, University of Murcia, Hospital Virgen de la ArrixacaLAIB room 2.52, Avda. Buenavista s/n, 30120, Murcia, Spain. dpascual@um.es.; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. dpascual@um.es.; CIBERCV, Madrid, Spain. dpascual@um.es. |
| Abstrakt: |
Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have shown to prevent heart failure progression, although the mechanisms remain poorly understood. Here we evaluated the effect of empagliflozin (EMPA, SGLT2i) in cardiac remodeling after myocardial infarction, the interplay with diabetes status and the role of cardiac GTP enzyme cyclohydrolase 1 (cGCH1). A rat model of diabetes (50 mg/kg streptozotocin, i.p.) was subjected to myocardial infarction and left ventricular systolic dysfunction, by ligation of the left anterior descending coronary artery. EMPA therapy significantly improved cardiac remodeling parameters and ameliorated processes of fibrosis and hypertrophy, in both non-diabetic and diabetic rats. This cardioprotective effect related with a significant increase in myocardial expression levels of cGCH1, which led to activation of nNOS and eNOS, and inhibition of iNOS, and subsequently resulted in increasing of NO levels and decreasing O 2 .- and nitrotyrosine levels. These effects were replicated in a cardiomyocyte biomechanical stretching diabetic model, where silencing cGCH1 blocked the preventive effect of EMPA. The beneficial effects were observed irrespective of diabetes status, although the magnitude was greater in presence of diabetes. Empagliflozin improves myocardial remodeling after myocardial infarction through overexpression of cGCH1, and irrespective of diabetes status. |
