CONTEXT: Mechanisms mediating the cardiovascular and renal protection exerted by SGLT2 inhibitors are still partially unknown. We investigated whether dapagliflozin modulates systemic and renal vascular function and structure, and induces epigenetic modifications. SUBJECTS AND METHODS: Forty hypertensive patients with type 2 diabetes were randomly assigned to 4-week treatment with dapagliflozin 10 mg or hydrochlorothiazide (HCT) 12.5 mg. Routine analyses; plasma renin activity; aldosterone, catecholamine, and 24-hour urinary electrolyte levels; flow-mediated dilation (FMD) of the brachial artery; carotid-femoral pulse-wave velocity (PWV); augmentation index; and resistive index and dynamic renal resistive index (DRIN) were measured at baseline and after treatment. Circulating miRNAs (miRs) related to heart failure (miR30e-5p, miR199a-3p), endothelial dysfunction (miR27b and miR200b), and renal function (miR130b-3p, miR21-5p) were assessed and related to the effects of treatments. RESULTS:Dapagliflozin and HCT marginally lowered blood pressure. Fasting glucose was lowered, whereas 24-hour diuresis, glycosuria, and osmolar clearance were increased by dapagliflozin (P < 0.001 for all), without affecting sodium excretion and glomerular filtration rate. Magnesium levels significantly increased after dapagliflozin treatment (P = 0.02). Neither dapagliflozin nor HCT modified FMD or PWV. DRIN did not vary in the dapagliflozin group, whereas it increased in the HCT group (P = 0.047 for time by treatment interaction). Both treatments induced variations in the expression of some miRs; dapagliflozin, but not HCT, significantly up-regulated miR30e-5p and downregulated miR199a-3p. CONCLUSION: A putative epigenetic regulation of the protecting cardiovascular effect exerted by SGLT2 inhibitors was found. Dapagliflozin might exert nephroprotection by preserving renal vasodilating capacity.
RCT Entities:
CONTEXT: Mechanisms mediating the cardiovascular and renal protection exerted by SGLT2 inhibitors are still partially unknown. We investigated whether dapagliflozin modulates systemic and renal vascular function and structure, and induces epigenetic modifications. SUBJECTS AND METHODS: Forty hypertensivepatients with type 2 diabetes were randomly assigned to 4-week treatment with dapagliflozin 10 mg or hydrochlorothiazide (HCT) 12.5 mg. Routine analyses; plasma renin activity; aldosterone, catecholamine, and 24-hour urinary electrolyte levels; flow-mediated dilation (FMD) of the brachial artery; carotid-femoral pulse-wave velocity (PWV); augmentation index; and resistive index and dynamic renal resistive index (DRIN) were measured at baseline and after treatment. Circulating miRNAs (miRs) related to heart failure (miR30e-5p, miR199a-3p), endothelial dysfunction (miR27b and miR200b), and renal function (miR130b-3p, miR21-5p) were assessed and related to the effects of treatments. RESULTS:Dapagliflozin and HCT marginally lowered blood pressure. Fasting glucose was lowered, whereas 24-hour diuresis, glycosuria, and osmolar clearance were increased by dapagliflozin (P < 0.001 for all), without affecting sodium excretion and glomerular filtration rate. Magnesium levels significantly increased after dapagliflozin treatment (P = 0.02). Neither dapagliflozin nor HCT modified FMD or PWV. DRIN did not vary in the dapagliflozin group, whereas it increased in the HCT group (P = 0.047 for time by treatment interaction). Both treatments induced variations in the expression of some miRs; dapagliflozin, but not HCT, significantly up-regulated miR30e-5p and downregulated miR199a-3p. CONCLUSION: A putative epigenetic regulation of the protecting cardiovascular effect exerted by SGLT2 inhibitors was found. Dapagliflozin might exert nephroprotection by preserving renal vasodilating capacity.
Authors: Ikaro Breder; Jessica Cunha Breder; Isabella Bonilha; Daniel B Munhoz; Sheila T Kimura Medorima; Daniela C Oliveira; Helison R do Carmo; Camila Moreira; Anatol Kontush; Francesca Zimetti; Ilaria Zanotti; Luiz Sergio F Carvalho; Wilson Nadruz; Elza Muscelli; Thiago Quinaglia; Andrei C Sposito Journal: Ther Adv Chronic Dis Date: 2020-09-28 Impact factor: 5.091
Authors: Julio M Martinez-Moreno; Miguel Fontecha-Barriuso; Diego Martin-Sanchez; Juan Guerrero-Mauvecin; Elena Goma-Garces; Beatriz Fernandez-Fernandez; Sol Carriazo; Maria D Sanchez-Niño; Adrian M Ramos; Marta Ruiz-Ortega; Alberto Ortiz; Ana B Sanz Journal: Int J Mol Sci Date: 2020-06-09 Impact factor: 5.923
Authors: Andrei C Sposito; Ikaro Breder; Alexandre A S Soares; Sheila T Kimura-Medorima; Daniel B Munhoz; Riobaldo M R Cintra; Isabella Bonilha; Daniela C Oliveira; Jessica Cunha Breder; Pamela Cavalcante; Camila Moreira; Filipe A Moura; Jose Carlos de Lima-Junior; Helison R P do Carmo; Joaquim Barreto; Wilson Nadruz; Luiz Sergio F Carvalho; Thiago Quinaglia Journal: Cardiovasc Diabetol Date: 2021-03-26 Impact factor: 9.951