Comparative Effects of Three Sulfonylureas (Glibenclamide, Glimepiride, and Gliclazide) on Proliferation and Migration of Vascular Smooth Muscle Cells.

Rui Zhang; Zhiwei Zou; Xiaojun Zhou; Xue Shen; Zhengyuan Fan; Tianyue Xie; Chunmei Xu; Lin Liao; Jianjun Dong

Background/Aims: Diabetes affects the entire vascular system and accelerates atherosclerosis and ischemia. Percutaneous transluminal angioplasty with or without stenting is the main therapeutic strategies; however, the restenosis rate is high in diabetics. Sulfonylureas (SUs) are widely prescribed agents for the treatment of type 2 diabetes (T2DM) and function by interacting with sulfonylurea receptors (SURs), which also exists in vascular smooth muscle cells (VSMCs), give rise to the potential that SUs influence VSMCs. The proliferation and migration of VSMCs play important roles in the formations of primary stenosis and restenosis, especially the latter. However, there are no data about the exact effects of SUs on these processes. Methods: Human aortic smooth muscle cells (HASMCs) were exposed to SUs prior to exposure to 30mM glucose. Cell proliferation was detected by CCK8 assay. Cell migration was detected by wound healing assay and transwell assay. Protein expression was determined by immunofluorescence and western blot. Diazoxide was used to evaluate the role of KATP channel in these processes. Results: The proliferation and migration of HASMCs were significantly aggravated by glibenclamide and glimepiride, and their effects were reversed by diazoxide. In contrast, above characteristics of HASMCs were apparently inhibited by gliclazide, and this was maintained after opening the KATP channel. Conclusion: These results imply that KATP channels play an important part in proliferation and migration of VSMCs induced by glibenclamide and glimepiride. In contrast, the inhibitory effect of gliclazide on VSMCs appeared to have more potential for the prevention of vascular obstructive diseases in T2DM.

SULFONYLUREAS; GLIBENCLAMIDE; GLICLAZIDE; VASCULAR smooth muscle; ATHEROSCLEROSIS; CELL proliferation

Cellular Physiology & Biochemistry (Cell Physiol Biochem Press GmbH & Co. KG), 2019, Vol 52, Issue 1, p16

1015-8987

Academic Journal

10.33594/000000002