Empagliflozin improves post-infarction cardiac remodeling through GTP enzyme cyclohydrolase 1 and irrespective of diabetes status
Por:
Lopez, MDA, Lax, A, Vicente, AH, Guillen, ES, Hernandez-Martinez, A, del Palacio, MJF, Genis, AB and Figal, DAP
Publicada:
11 ago 2020
Resumen:
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.
Filiaciones:
Lopez, MDA:
Univ Murcia, Biomed Res Inst Virgen de La Arrixaca IMIB Arrixa, Ctra Madrid Cartagena S-N, Murcia 30120, Spain
Lax, A:
Univ Murcia, Biomed Res Inst Virgen de La Arrixaca IMIB Arrixa, Ctra Madrid Cartagena S-N, Murcia 30120, Spain
Vicente, AH:
Univ Murcia, IMIB Arrixaca, Hosp Virgen de la Arrixaca, Cardiol Dept, Murcia, Spain
Guillen, ES:
Univ Murcia, Hosp Virgen de La Arrixaca, Endocrinol Dept, Murcia, Spain
Hernandez-Martinez, A:
Univ Murcia, Hosp Virgen de La Arrixaca, Endocrinol Dept, Murcia, Spain
del Palacio, MJF:
Univ Murcia, Vet Teaching Hosp, Vet Med & Surg Dept, Murcia, Spain
:
Hosp Univ German Trias & Puyol, CIBERCV, Heart Inst, Badalonamadrid, Spain
Figal, DAP:
Univ Murcia, IMIB Arrixaca, Cardiol Dept, Hosp Virgen de la ArrixacaLAIB Room 2-52, Murcia 30120, Spain
Ctr Nacl Invest Cardiovasc CNIC, Madrid, Spain
CIBERCV, Madrid, Spain
Green Published, gold
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