Sitagliptin attenuates high glucose-induced alterations in migration, proliferation, calcification and apoptosis of vascular smooth muscle cells through ERK1/2 signal pathway.

Lili Shi,Changqing Xu,Ying Liu,Ye Ji,Xiaoyan Jiang,Ying Xu,Dandan Liu,Yang Cao

doi:10.18632/oncotarget.20417

Abstract

Background/AimsThis study investigated the effects of sitagliptin on migration, proliferation, calcification and apoptosis of vascular smooth muscle cells (VSMCs) under high glucose (HG) conditions.MethodsVSMCs were isolated from the thoracic aorta of Sprague Dawley rats. The cultured VSMCs were subjected to control medium, mannitol medium, HG medium (25 mM), pretreatment with 200 nM sitagliptin in control or HG medium, or the ERK1/2 inhibitor PD98059 in HG medium. Cell proliferation, migration, apoptosis and calcification were determined.ResultsHG conditions promoted the proliferation, migration, calcification and impairment of apoptosis in VSMCs compared with controls (P<0.05). Pretreatment with sitagliptin effectively attenuated proliferation, migration, calcification of cells and increased apoptosis of HG-cultured VSMCs as compared with the HG group (P<0.05). Culture with HG resulted in the up-regulation of p-ERK1/2 in VSMCs, whereas sitagliptin pretreatment could inhibit HG-induced p-ERK1/2 expression. In addition, the ERK1/2 inhibitor PD98059, inhibited proliferation, migration, calcification and promoted the apoptosis of HG-cultured VSMCs compared with the HG group (P<0.05).ConclusionThe effects of sitagliptin on VSMC under high glucose condition were achieved through ERK1/2 signaling pathways.

Highlights

Atherosclerosis (AS) is one of the most common cardiovascular complications of diabetes, and remains the leading cause of death in diabetic patients [1]
Culture with high glucose (HG) resulted in the up-regulation of p-ERK1/2 in Vascular smooth muscle cell (VSMC), whereas sitagliptin pretreatment could inhibit HG-induced p-ERK1/2 expression
The ERK1/2 inhibitor PD98059, inhibited proliferation, migration, calcification and promoted the apoptosis of HG-cultured VSMCs compared with the HG group (P

Summary

Introduction

Atherosclerosis (AS) is one of the most common cardiovascular complications of diabetes, and remains the leading cause of death in diabetic patients [1]. Chronic hyperglycemia leads to increased production of reactive oxygen species (ROS), stimulating the proliferation of VSMCs and migration www.impactjournals.com/oncotarget to arterial intima [3, 4]. Excessive proliferation and impaired apoptosis of VSMCs contribute to massive deposition of VSMCs in the vascular intima and medial atherosclerotic plaque [5], thereby leading to atherosclerotic vascular remodeling. Proliferation, calcification and a reduction in apoptosis of VSMCs under hyperglycemic conditions are involved in the formation of atherosclerotic plaque formation in diabetes mellitus [3,4,5,6, 10], it is possible to treat diabetic atherosclerosis by inhibiting hyperglycemia-triggered events in VSMCs

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Conclusion