Sodium-Glucose Cotransporter 2 Inhibitors regulate vascular cell function
Abstract
[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Vascular disease is the major cause of morbidity and mortality in diabetic patients. Although numerous factors contribute to the development of diabetes-associated vascular disease, the malfunction of vascular smooth cells (SMCs) and endothelial cells (ECs) plays a fundamental role. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are the latest class of glucose-lowering agents. By blocking glucose uptake in the proximal tubules of the nephron they induce glycosuria leading to decreases in circulating glucose. Notably, recent long-term, large scale cardiovascular outcome trials with SGLT2 inhibitors demonstrated benefits beyond glycemic control with a significant reduction in cardiovascular disease and mortality in type 2 diabetic patients. However, among the SGLT2 inhibitors, canagliflozin caused a 2-fold increase in limb amputations that was not seen with other SGLT2 inhibitors. The decrease in mortality by SGLT2 inhibitors has been attributed to improvements in renal function, energy balance, body weight, and blood pressure, but direct effects by these drugs on vascular cells have not been considered. In the present study, we investigated the effect of three US Food and Drug Administration approved SGLT2 inhibitors on cultured vascular cell function. Treatment of human umbilical vein ECs with canagliflozin (0-50[mu]M) resulted in a potent concentration-dependent inhibition in cell proliferation and…
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