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Amelioration of endothelial dysfunction by sodium glucose co-transporter 2 inhibitors: pieces of the puzzle explaining their cardiovascular protection
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  • Xiaoling Li,
  • Benedikt Preckel,
  • Jeroen Hermanides,
  • Markus Hollmann,
  • Coert Zuurbier,
  • Nina Weber
Xiaoling Li
Amsterdam UMC Location AMC

Corresponding Author:[email protected]

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Benedikt Preckel
Amsterdam UMC Location AMC
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Jeroen Hermanides
Amsterdam UMC Location AMC
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Markus Hollmann
Amsterdam UMC Location AMC
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Coert Zuurbier
Amsterdam UMC Location AMC
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Nina Weber
Amsterdam UMC Location AMC
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Sodium glucose co-transporter 2 inhibitors (SGLT-2i’s) significantly improve cardiovascular outcome in both diabetic and non-diabetic patients. Preclinical studies suggest that SGLT-2i’s directly affect endothelial function in a glucose-independent manner. The effects of SGLT-2i’s include reduction of oxidative stress and inflammatory reaction in endothelial cells. Furthermore, SGLT2i’s have been shown to restore endothelial-related vasodilation and to regulate angiogenesis. The favorable cardiovascular effects of SGLT-2i’s might be mediated via multiple pathways: 1) by inhibition of the overactive sodium-hydrogen exchanger; 2) by reduction of nicotinamide adenine dinucleotide phosphate oxidases expression; 3) by alleviation of mitochondrial injury; 4) by the suppression of inflammatory-related signaling pathways (e.g. by affecting nuclear factor kappa beta); 5) by modulation of glycolysis, as well as 6) by restoring impaired nitric oxide bioavailability. This review focuses on the most recent progress and existing gaps in preclinical investigations concerning the direct effects of SGLT-2i’s on endothelial dysfunction and their underlying mechanisms.
12 Jan 2022Submitted to British Journal of Pharmacology
15 Jan 2022Submission Checks Completed
15 Jan 2022Assigned to Editor
19 Jan 2022Reviewer(s) Assigned
11 Feb 2022Review(s) Completed, Editorial Evaluation Pending
14 Feb 2022Editorial Decision: Revise Minor
04 Mar 20221st Revision Received
08 Mar 2022Submission Checks Completed
08 Mar 2022Assigned to Editor
11 Mar 2022Reviewer(s) Assigned
18 Mar 2022Review(s) Completed, Editorial Evaluation Pending
30 Mar 2022Editorial Decision: Accept
07 Apr 2022Published in British Journal of Pharmacology. 10.1111/bph.15850