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The effect of SGLT2 inhibitors on the endothelium and the microcirculation: from bench to bedside and beyond

Kyriakos Dimitriadis1, Eleni Adamopoulou1, Nikolaos Pyrpyris1

  • 1First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27, Athens, Greece.

European Heart Journal. Cardiovascular Pharmacotherapy
|July 27, 2023
PubMed

Insights

Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular health by benefiting endothelial function and microcirculation. These drugs attenuate dysfunction through multiple mechanisms, offering cardiovascular protection.

Area of Science:

  • Cardiovascular Medicine
  • Pharmacology
  • Endothelial Biology

Background:

  • Sodium-glucose cotransporter 2 (SGLT2) inhibitors are established for cardiovascular benefits, particularly in heart failure, regardless of diabetes status.
  • The precise mechanisms underlying these cardiovascular effects, especially on the endothelium and microcirculation, require further elucidation.
  • Understanding these mechanisms is crucial for optimizing SGLT2 inhibitor therapy and exploring new therapeutic avenues.

Approach:

  • A comprehensive literature review was performed using MEDLINE/PubMed to synthesize preclinical and clinical data.
  • The review links basic science findings ('bench') with clinical observations ('bedside') on SGLT2 inhibitors' effects.
  • The study identifies current knowledge gaps and proposes future research directions.

Key Points:

  • Preclinical studies demonstrate that SGLT2 inhibitors directly enhance endothelial function independent of glucose levels.
  • Observed effects include improved vasodilation, increased nitric oxide (NO) production, better mitochondrial function, and reduced oxidative stress/inflammation.
  • Clinical data support beneficial endothelial effects, but findings on microcirculation remain inconsistent.

Conclusions:

  • SGLT2 inhibitors mitigate endothelial and microvascular dysfunction through a multifaceted mechanism.
  • These actions contribute significantly to the observed cardiovascular benefits of SGLT2 inhibitors.
  • Further research is warranted to fully clarify the impact on microcirculation.
Abstract

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