Background/aims: This study investigated the effects of sitagliptin on migration, proliferation, calcification and apoptosis of vascular smooth muscle cells (VSMCs) under high glucose (HG) conditions.
Methods: VSMCs 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.
Results: HG 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).
Conclusion: The effects of sitagliptin on VSMC under high glucose condition were achieved through ERK1/2 signaling pathways.
Keywords: atherosclerosis; diabetes; dipeptidyl peptidase-4 inhibitor; high glucose; vascular smooth muscle cells.