Table 2.
The direct effect of sodium-glucose co-transporter-2 inhibitors on endothelial function in cell culture
| Cell lines | Drug (dose) | Stimulant (dose) | Major finding | References |
|---|---|---|---|---|
| HCAECs | Empagliflozin and dapagliflozin (1 μM)/2 h | TNFα (10 ng/ml)/ 4–24 h | ↓ ROS level in TNFα-stimulated cells | [59] |
| HUVECs | Empagliflozin and dapagliflozin (1 μM)/2 h | TNFα (10 ng/ml)/4–24 h | ↑ NO bioavailability in TNFα-stimulated cells | [59] |
| Porcine coronary artery endothelial cells | Empagliflozin (1–100 nmol/l)/30 min |
HG (25 mmol/l) or H2O2 (100 μmol/l)/24 h |
↓ SA‐β‐gal in HG‐treated cells ↓ p21 and p16 expression level in HG‐treated cells ↓ eNOS and VCAM‐1 mRNA and protein expression level in HG‐treated cells ↑ mRNA SGLT-1 and SGLT-2 expression in H2O2‐ and HG‐treated ECs |
[37] |
| HAAECs | Empagliflozin (50 μM)/24 h | Statically cultured or subjected to a steady wall shear stress of 10 dyne/cm |
↓ Roundness of the cells under static conditions ↓ TNFα-associated HAAEC-NB4 cell adhesion under static and flow conditions ↓ NB4-HAAEC adhesion under static and perfused conditions ↑ HS intensity level under static and flow culture conditions in heparinase III-treated cells |
[60] |
| HUVECs | Canagliflozin (0–50 μM), empagliflozin (0–50 μM), dapagliflozin (0–50 μM)/3 days |
↓ DNA synthesis in a dose-dependent manner by dapagliflozin ↓ Proliferation in a dose-dependent manner by three SGLT-2 inhibitors Canagliflozin disrupts cell cycle progression, ↓ cyclin A expression and the phosphorylation of retinoblastoma protein |
[61] | |
| Murine endothelial cells | Empagliflozin (25 nM-10 μM)/24 h | HG (25 mM)/24 h |
↓ Src-kinase, EGF receptor-kinase, protein kinase-C and Rho-kinase ↑ PAR2-mediated vasodilation in tissues cultured under hyperglycaemic conditions |
[62] |
| HUVECs | Canagliflozin (10 μM)/30 min | IL-1β (10 ng/ml) for 6 h | ↓ IL-6 and MCP-1 protein and MRNA expression | [45] |
| HAECs | Canagliflozin (10 μM)/15 min | IL-1β (5 ng/ml) for 4 h | ↓ IL-6 and MCP-1 protein and mRNA expression | [45] |
| HUVECs |
Dapagliflozin (1.0–5.0 nM)/24 h Dapagliflozin (100 nM)/24 h |
TNFα (10 ng/ml) or HG (10–30 mM) for 24 h |
↓ ICAM-1 & VCAM-1 protein levels ↑ PAI-1 protein ↓ ICAM-1, PAI-1 mRNA and protein expression in hyperglycemia-treated cells |
[26] |
| HUVECs | Empagliflozin (0.1–100 μM) | VEGF (10 ng/ml) for 1 h | Neutral effect of the drug on endothelial cell proliferation | [35] |
| HUVECs | Empagliflozin (1 or 10 μM)/6 days | Ach (1 μM)/30 min after cultured under HG (30 mM) | ↑ viability of hyperglycemic endothelial cells | [57] |
EGF Epidermal growth factor, H202 hydrogen peroxide, HAAECs human abdominal 2a aortic endothelial cells, HAECs human aortic endothelial cells, HCAECs human coronary artery endothelial cells, HG high glucose, HUVECs human umbilical vein endothelial cell, NO nitric oxide, PAI-1 plasminogen, PAR-2 proteinase activated receptor 2, SGLT-2 sodium-glucose co-transporter-2