Clinical care and other categories posters: Audit

Aims: Previous in vitro studies have reported that acute stimulation of endothelial cells with canagliflozin directly inhibits IL-1β-stimulated secretion of selected pro-inflammatory and pro-atherogenic mediators.This finding implicates a potential direct anti-inflammatory, pleotropic effect of SGLT inhibitor therapy on vascular function.We aim to assess whether additional sodium-glucose co-transporter-2 (SGLT2) inhibitors (canagliflozin, dapagliflozin or empagliflozin) confer a protective effect against the pro-inflammatory stimuli TNF-α and IFN-Υ.Methods: Human umbilical vein endothelial cells (HUVECs) were pre-incubated in the presence or absence of canagliflozin (1 μM, 10 μM, and 100 μM), dapagliflozin (1 μM, 10 μM and 100 μM) and empagliflozin (1 μM, 10 μM, and 100 μM) for one hour.The cells were then stimulated with TNF-α (10 ng/mL) and IFN-Υ (10 ng/ml) for 24 hours.Subsequently, the expression level of IL-6 and was analysed using Quantikine ELISA kits as per the manufacturer's instructions.Results: The pro-inflammatory cytokines TNF-α and IFN-Υ and significantly induced expression of IL-6 in HUVECs compared to controls (p = <0.0001).The stimulatory effects of TNF-α and IFN-Υ on IL-6 expressions were significantly inhibited by canagliflozin 1 μM, 10 μM, and 100 μM (p = 0.0099, p < 0.0001, and p < 0.0001, respectively, compared to inflammatory stimulus alone).No significant inhibitory effects of dapagliflozin and empagliflozin on IL-6 expression were observed.Conclusions: This result indicates that canagliflozin directly inhibits endothelial pro-inflammatory cytokines secretions.This striking anti-inflammatory of this SGLT2 inhibitor therapy may explain the mechanism of cardiovascular benefits with canagfliflozin and merits further mechanistic research.