N-4-Tert-Butyl Benzyl Haloperidol Chloride Suppresses Ca-dependent Egr-1 Expression and Subsequently Inhibits Vascular Smooth Muscle Cell Proliferation Induced by Angiotensin II

Yicun Chen; Jinhong Zheng; Yanmei Zhang; Jinzhi Wang; Qing Liu; Zhanqin Huang; Fenfei Gao; Yanqiong Zhou; Ganggang Shi
February 2009
Cellular Physiology & Biochemistry (Karger AG);2009, Vol. 23 Issue 4-6, p295
Academic Journal
Background: N-4-Tert-Butyl benzyl haloperidol chloride (C3) was a novel calcium antagonist synthesized in our laboratory. The present study is to explore the effect of C3 on vascular smooth muscle cell proliferation and the mechanism involved. Methods: The effects of C3 on Ang II-induced cytosolic free Ca2+ concentration change, VSMC proliferation, the key early growth response factor 1 (Egr-1) were evaluated by laser scanning confocal microscopy, microtiter tetrazolium (MTT) proliferation assay, flow cytometry analysis, Western blot and RT-PCR analysis, respectively. An extracellular Ca2+ chelator EGTA and antisense Egr-1 oligodeoxyribonucleotides (ODNs) were used to establish the relation between Ca2+-dependent Egr-1 expression induced by Ang II and VSMC proliferation. Results: C3 attenuated the Ang II-induced extracellular Ca2+ influx, inhibited VSMCs proliferation and arrested VSMCs in G1-phase. C3 also triggered a significant reduction in PDGF-A and cyclin D1, Cdk2 along with an overexpression of p21Cip1. Antisense Egr-1 ODNs inhibited VSMCs proliferation, which was related to G1-phase arrest, due to inhibiting the expression of Egr-1 and C3 inhibited the overexpression of Egr-1. Conclusion: Egr-1 may play a key role in Ang II-induced proliferation of VSMCs. C3 inhibits vascular smooth muscle cell proliferation and the mechanism is involved with the inhibition of over-expression of Egr-1. Copyright © 2009 S. Karger AG, Basel


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