Abstract
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.
Original language | English |
---|---|
Pages (from-to) | 4047-4062 |
Number of pages | 16 |
Journal | British journal of pharmacology |
Volume | 179 |
Issue number | 16 |
Early online date | 2022 |
DOIs | |
Publication status | Published - Aug 2022 |
Keywords
- endothelial dysfunction
- inflammation
- reactive oxygen species
- sodium glucose co-transporter 2 inhibitors
- sodium-hydrogen exchanger