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The Effects of Dapagliflozin on Systemic and Renal Vascular Function Display an Epigenetic Signature

Anna Solini1, Marta Seghieri2, Livia Giannini2

  • 1Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy.

The Journal of Clinical Endocrinology and Metabolism
|June 5, 2019
PubMed
Abstract

Insights

Sodium-glucose cotransporter 2 (SGLT2) inhibitors like dapagliflozin may offer cardiovascular and kidney protection through epigenetic modifications. Dapagliflozin appears to preserve renal vasodilating capacity, contributing to nephroprotection.

Area of Science:

  • Cardiovascular research
  • Nephrology
  • Endocrinology

Background:

  • The precise mechanisms behind the cardiovascular and renal protective effects of SGLT2 inhibitors remain incompletely understood.
  • Investigating these mechanisms is crucial for optimizing treatment strategies in patients with type 2 diabetes and hypertension.

Purpose of the Study:

  • To determine if dapagliflozin influences systemic and renal vascular function and structure.
  • To explore whether dapagliflozin induces epigenetic modifications, specifically changes in circulating microRNAs (miRs).

Main Methods:

  • A 4-week randomized trial comparing dapagliflozin (10 mg) with hydrochlorothiazide (HCT, 12.5 mg) in 40 hypertensive patients with type 2 diabetes.
  • Comprehensive assessments included routine analyses, hormonal levels, urinary electrolytes, flow-mediated dilation (FMD), pulse-wave velocity (PWV), and dynamic renal resistive index (DRIN).
  • Circulating miRs associated with heart failure, endothelial dysfunction, and renal function were analyzed.

Main Results:

  • Both dapagliflozin and HCT showed modest blood pressure reduction. Dapagliflozin increased diuresis, glycosuria, and osmolar clearance, with a significant rise in magnesium levels, but did not alter sodium excretion or glomerular filtration rate.
  • Neither drug affected FMD or PWV. Dapagliflozin preserved DRIN, unlike HCT which increased it. Specific miRs related to heart failure were modulated by dapagliflozin, with up-regulation of miR30e-5p and down-regulation of miR199a-3p.

Conclusions:

  • Dapagliflozin may exert cardiovascular protective effects through putative epigenetic regulation.
  • The drug appears to offer nephroprotection by maintaining renal vasodilating capacity.

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