BACKGROUND: N-4-Tert-Butyl benzyl haloperidol chloride (C(3)) was a novel calcium antagonist synthesized in our laboratory. The present study is to explore the effect of C(3) on vascular smooth muscle cell proliferation and the mechanism involved. METHODS: The effects of C(3) on Ang II-induced cytosolic free Ca(2+) 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 Ca(2+) chelator EGTA and antisense Egr-1 oligodeoxyribonucleotides (ODNs) were used to establish the relation between Ca(2+)-dependent Egr-1 expression induced by Ang II and VSMC proliferation. RESULTS: C(3) attenuated the Ang II-induced extracellular Ca(2+) influx, inhibited VSMCs proliferation and arrested VSMCs in G(1)-phase. C(3) 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 G(1)-phase arrest, due to inhibiting the expression of Egr-1 and C(3) inhibited the overexpression of Egr-1. CONCLUSION: Egr-1 may play a key role in Ang II-induced proliferation of VSMCs. C(3) 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.
BACKGROUND:N-4-Tert-Butyl benzyl haloperidol chloride (C(3)) was a novel calcium antagonist synthesized in our laboratory. The present study is to explore the effect of C(3) on vascular smooth muscle cell proliferation and the mechanism involved. METHODS: The effects of C(3) on Ang II-induced cytosolic free Ca(2+) 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 Ca(2+) chelator EGTA and antisense Egr-1 oligodeoxyribonucleotides (ODNs) were used to establish the relation between Ca(2+)-dependent Egr-1 expression induced by Ang II and VSMC proliferation. RESULTS: C(3) attenuated the Ang II-induced extracellular Ca(2+) influx, inhibited VSMCs proliferation and arrested VSMCs in G(1)-phase. C(3) 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 G(1)-phase arrest, due to inhibiting the expression of Egr-1 and C(3) inhibited the overexpression of Egr-1. CONCLUSION:Egr-1 may play a key role in Ang II-induced proliferation of VSMCs. C(3) 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.