Canagliflozin Inhibits Human Endothelial Cell Proliferation and Tube Formation

In conclusion, the present study identified canagliflozin as a potent inhibitor of human EC proliferation. The anti-proliferative action of canagliflozin is observed in ECs isolated from both the venous and arterial circulation, and is partly due to the blockade of cyclin A expression. In addition, this study found that canagliflozin inhibits tube formation in cultured ECs and mouse aortic rings. Notably, these actions are specific for canagliflozin and not seen with other SGLT2 inhibitors. The ability of canagliflozin to exert these pleiotropic effects on EC function may contribute to both the adverse and salutary actions of this drug on cardiovascular function in T2DM patients. Ethics Statement This study was approved by the institutional Animal Care-Use Committees of the University of Missouri and the Truman VA Hospital (Columbia, MO, USA) and performed in accordance with the National Research Council’s Guide 152 for the Care and Use of Laboratory Animal. Author Contributions GB, SMB, SBB, KP, LM-L, and WD participated in research design. GB, SMB, ZD, and KP conducted experiments and performed data analysis. GB, SMB, SBB, LM-L, KP, and WD wrote or contributed to writing of the manuscript. Funding This work was supported by the American Diabetes Association [#1-17-IBS-290 to WD], the Department of Veterans Affairs BLR&D [IK2 BX002030 to SBB], and the National Institutes of Health [HL136386 to SBB and HL088105 to LM-L]. This work was also supported...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research