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Effects of KTJ740, a novel antithrombotic agent, on platelet-derived growth factor-induced rat aortic smooth muscle cell proliferation and cell cycle progression

Title
Effects of KTJ740, a novel antithrombotic agent, on platelet-derived growth factor-induced rat aortic smooth muscle cell proliferation and cell cycle progression
Authors
Kim T.-J.Jeon J.Jin Y.-R.Son D.-J.Yoo H.-S.Hong J.-T.Ryu C.-K.Shin H.-S.Lee K.-H.Yun Y.-P.
Ewha Authors
유충규
SCOPUS Author ID
유충규scopus
Issue Date
2007
Journal Title
Journal of Cardiovascular Pharmacology
ISSN
0160-2446JCR Link
Citation
vol. 49, no. 5, pp. 280 - 286
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Hyperproliferation of platelet-derived growth factor (PDGF)-BB-induced vascular smooth muscle cell (VSMC) is a hallmark of atherosclerosis and related vascular disorders. In the previous study, we reported that KTJ740 [2-chloro-3-(4-(ethylcarboxy)-phenyl)-amino-1,4-naphthoquinone], a newly synthesized vitamin K derivative, has potent antithrombotic effects in mice and antiplatelet activity in vitro and ex vivo. In the present study, we have tested that KTJ740 could inhibit PDGF-BB-stimulated VSMC proliferation. We have examined the potential inhibitory effect of this compound on rat aortic smooth muscle cells (RASMCs). Our results show that this compound significantly inhibits PDGF-BB-stimulated RASMC number and DNA synthesis in a concentration-dependent manner. Furthermore, we have examined its effect on cell cycle progression by flow cytometry. KTJ740 treatment resulted in a significant arrest in cell cycle progression of RASMCs induced by PDGF-BB, and this effect was achieved by suppressing activation of PDGF-β receptor (PDGF-Rβ) tyrosine kinase pathway. These results suggest that a possibility of KTJ740 can be a potential agent to control vascular disorders and its antiproliferative mechanism may be mediated through PDGF-Rβ tyrosine kinase-dependent signaling pathway. © 2007 Lippincott Williams & Wilkins, Inc.
DOI
10.1097/FJC.0b013e3180399448
Appears in Collections:
약학대학 > 약학과 > Journal papers
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