Mechanisms of the inhibitory effect of platonin on rat vascular smooth muscle cell proliferation

• Main Authors: Shiao-Yun Tseng, 曾筱勻
• Other Authors: Joen-Rong Sheu
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/84553386587846286922

碩士 === 臺北醫學大學 === 藥理學研究所 === 94 === Abnormal proliferation of vascular smooth muscle cells (VSMCs) results in neointima plays an important role in many coronary diseases including atherosclerosis and restenosis. This research has shown the inhibitory mechanisms of platonin (4,4',4''-Trimethyl-3,3',3''-Trihepthyl-7-(2''-thiazolyl)-2,2',-Trimethine Thiazolocyanine-3,3''-Diiodide) on VSMCs proliferation. By MTT assay, we found that platonin inhibited PDGF-BB-induced vascular smooth muscle cells proliferation in a concentration dependent manner. Then we observed the morphological changes of VSMCs by microscopy. VSMCs were shrinked and apoptotic body were formed. Using flow cytometry, we find that platonin increased the sub-G1 phase of the cell cycle. Thus, we propose that platonin may inhibit PDGF-BB-induced vascular smooth muscle cells proliferation and even increase the apoptosis of VSMCs. And then we investigated the mechanism of platonin inhibiting PDGF-BB-induced vascular smooth muscle cells proliferation. We found that platonin did not inhibit the phosphorylation of Akt and ERK, however platonin could inhibit the phosphorylation of p38 and JNK significantly. JNK inhibition may play an important role in this mechanism according to c-jun inhibition of platonin. We will further focus on investigating the effects of platonin on molecular regulation of cell cycle and apoptosis. In addition to its anti-inflammatory and anti-oxidation activities, this research showed that platonin inhibited VSMCs proliferation. Because of the anti-proliferation effect of platonin, the further efforts to evaluate if platonin exhibits anti-neointimal formation and anti-restenosis effect.