Universitas Indonesia Conferences, Asian Federation for Pharmaceutical Sciences (AFPS) 2019

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Effect of novel compound on the proliferation and migration of vascular smooth muscle cells
Jun-Hwan Jo, Hyun-Soo Park, Eunju Yun, Gyu-yong Song, Chang-seon Myung

Last modified: 2019-06-16


Background: Vascular smooth muscle cells (VSMCs) function in the contraction and elasticity of the blood vessels in the body. However, abnormal proliferation and migration of VSMCs can cause vascular restenosis and atherosclerosis. Objective: This study was designed to investigate the effect of a novel compound (EJ-CSM15) on the proliferation and migration of VSMCs. Materials and Methods: VSMC proliferation was measured using both colorimetric MTT assay and direct cell counting in platelet-derived growth factor (PDGF) BB-induced VSMCs. Cell cycle progression was examined using flow cytometer, and the expression and phosphorylation of proteins was determined by immunoblotting assay. Animal experiment using balloon-injured rats were carried out using SD rats. A scratch wound-healing migration assay and gelatin zymography were performed. Results: EJ-CSM15 significantly inhibited PDGF-stimulated proliferation and DNA synthesis, and arrested the PDGF-stimulated progression through G0/G1 to S phase of cell cycle supported by the suppression of retinoblastoma protein (pRb) phosphorylation and cyclin D1/E, cyclin-dependent kinase (CDK) 2/4 and proliferative cell nuclear antigen (PCNA) expression. This compound dose-dependently inhibited the PDGF-stimulated phosphorylation of signal transducers and activators of transcription 3 (STAT3). The administration of 10 or 20 mg/kg EJ-CSM15 for 2 weeks diminished the neointima hyperplasia of the carotid artery in balloon-injured rats. In migration study, EJ-CSM15 reduced the PDGF-induced migration and the expression of matrix metalloproteinase-9 (MMP-9) in a dose-dependent manner. Moreover, the activity of MMP-9 was significantly inhibited by EJ-CSM15. Conclusion: Our findings suggest that the antiproliferative and antimigrative effects of EJ-CSM15 on PDGF-stimulated VSMCs are due to the blockade of STAT3 signaling pathways.


Key words: VSMC, Proliferation, Migration, STAT3, Neointima hyperplasia