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Amelioration of endothelial dysfunction by sodium glucose co‐transporter 2 inhibitors: pieces of the puzzle explaining their cardiovascular protection
Author(s) -
Li Xiaoling,
Preckel Benedikt,
Hermanides Jeroen,
Hollmann Markus W.,
Zuurbier Coert J.,
Weber Nina C.
Publication year - 2022
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.15850
Subject(s) - endothelial dysfunction , vasodilation , endothelium , pharmacology , medicine , angiogenesis , diabetes mellitus , oxidative stress , nicotinamide adenine dinucleotide phosphate , endocrinology , chemistry , biochemistry , enzyme , oxidase test
Sodium glucose co‐transporter 2 inhibitors (SGLT‐2is) improve cardiovascular outcomes in both diabetic and non‐diabetic patients. Preclinical studies suggest that SGLT‐2is directly affect endothelial function in a glucose‐independent manner. The effects of SGLT‐2is include decreased oxidative stress and inflammatory reactions in endothelial cells. Furthermore, SGLT2is restore endothelium‐related vasodilation and regulate angiogenesis. The favourable cardiovascular effects of SGLT‐2is could be mediated via a number of pathways: (1) inhibition of the overactive sodium‐hydrogen exchanger; (2) decreased expression of nicotinamide adenine dinucleotide phosphate oxidases; (3) alleviation of mitochondrial injury; (4) suppression of inflammation‐related signalling pathways (e.g., by affecting NF‐κB); (5) modulation of glycolysis; and (6) recovery of impaired NO bioavailability. This review focuses on the most recent progress and existing gaps in preclinical investigations concerning the direct effects of SGLT‐2is on endothelial dysfunction and the mechanisms underlying such effects.