Why the study?
Cardiovascular benefits of SGLT2 inhibitors are not fully understood, prompting evaluation of their influence on endothelial cell integrity interrupted by 25-OHC and associated VE-cadherin levels.
Do SGLT2 inhibitors restore endothelial cell integrity interrupted by 25-hydroxycholesterol in HUVECs?
Do SGLT2 inhibitors restore endothelial cell integrity interrupted by 25-hydroxycholesterol in HUVECs?
SGLT2 inhibitors restore endothelial integrity and VE-cadherin levels impaired by 25-hydroxycholesterol in vitro, offering a potential mechanism for their cardiovascular benefits.
Answers are grounded in this paper and cite their sources.
SGLT2i may protect endothelial barrier function in vitro; leaves open clinical translation and cardiovascular outcome impact.
SGLT2 (Sodium-glucose Cotransporter-2) inhibitors are newer glucose-lowering drugs with many cardiovascular benefits that are not fully understood yet. Endothelial integrity plays a key role in cardiovascular homeostasis. 25-hydroxycholesterol (25-OHC), which is a proatherogenic stimuli that impairs endothelial barrier functions. VE-cadherin is an endothelial-specific protein crucial in maintaining endothelial integrity. The aim of this study was to assess the influence of SGLT2i on the integrity of endothelial cells interrupted by 25-OHC. We also aimed to evaluate whether this effect is associated with changes in the levels of VE-cadherin. We pre-incubated HUVECs with 10 μg/mL of 25-hydroxycholesterol (25-OHC) for 4 h and then removed it and incubated endothelial cells with 1 μM of empagliflozin, 1 μM canagliflozin, or 1 μM dapagliflozin for 24 h. The control group included HUVECs cultured with the medium or with 25-OHC 10 μg/mL. The integrity of endothelial cells was measured by the RTCA-DP xCELLigence system, and VE-cadherin was assessed in confocal microscopy. Our results show that SGLT2 inhibitors significantly increase endothelial integrity in comparison to medium controls, and they improve endothelial cell integrity interrupted by 25-OHC. This effect is associated with significant improvements in VE-cadherin levels. SGLT2i: empagliflozin, canagliflozin, and dapagliflozin have a beneficial effect on the endothelial cell integrity and VE-cadherin levels reduced by 25-OHC.
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Pawlos et al. (2023) studied this question.
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