SAT-173 Antiproliferative Effect of Teneligliptin on Atherosclerosis in Vascular Smooth Muscle Cell

Abstract

Background and aims: In vivo and in vitro studies revealed that sitagliptin, linagliptin treatment suppressed proliferation of vascular smooth muscle cells (VSMCs). However, data are lacking regarding the effects of teneligliptin. Here, we demonstrate the effects of teneligliptin on VSMC proliferation and migration according to fluctuating glucose levels. Materials and methods: Primary cultures of male Otsuka Long-Evans Tokushima fatty (OLETF) rat VSMCs were obtained from enzymatically dissociated rat thoracic aorta. VSMCs with teneligliptin (100 μM) were incubated for 72 h with alternating normal (5.5 mmol/L) and high glucose (25 mmol/L) media every 12 h. The proliferation of VSMCs, proliferative and apoptotic molecular pathway and the migration of VSMC were analyzed with teneligliptin. Results: In MTT assay, teneligliptin attenuated the increase in cells pretreated with 100-μM teneligliptin 72 h prior to glucose fluctuation (F+T group) in comparison with fluctuation group (F group) (p-value, 0.005). The protein levels of phospho-MEK1/2 and phospho-ERK1/2 were significantly reduced in F+T group compared with F group (phospho-MEK1/2, p-value, 0.016; phospho-ERK1/2, p-value, 0.001). However no changes in the protein levels of caspase 3, Bcl-2, and phospho-Bad, Bax, Bcl-xL, were observed. In wound healing assay, migrated cell percentage was attenuated in F+T group (p-value, 0.043). phospho-BMK protein levels was also reduced in F+T group (p-value, 0.017). Conclusion: This study has demonstrated that teneligliptin significantly reduces the proliferation and migration of VSMCs in intermittent hyperglycemic condition.