کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5962705 1576126 2016 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
GT-repeat length polymorphism in heme oxygenase-1 promoter determines the effect of cilostazol on vascular smooth muscle cells
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
GT-repeat length polymorphism in heme oxygenase-1 promoter determines the effect of cilostazol on vascular smooth muscle cells
چکیده انگلیسی

BackgroundCilostazol, a potent type 3 phosphodiesterase inhibitor, is found to reduce neointimal formation by inhibiting vascular smooth muscle cell (VSMC) proliferation. The aim of this study is to investigate whether the inhibitory effect of cilostazol on VSMC proliferation is operated via heme oxygenase-1 (HO-1).Methods and resultsIn rat carotid arteries, cilostazol up-regulated HO-1 in the neointima of balloon-injured arteries. Treatment of human VSMCs with cilostazol enhanced the expression of HO-1, which was mainly regulated at the transcriptional level. Small interfering RNA knock-down of HO-1 attenuated the inhibitory effect of cilostazol on VSMC proliferation, suggesting the critical role of HO-1 in cilostazol effect. The transcriptional responsiveness of HO-1 to cilostazol was inversely correlated with the length of GT-repeat in human HO-1 promoter. Deletion and mutational analysis of HO-1 promoter along with chromatin immunoprecipitation showed that cyclic AMP response element (CRE)-binding protein (CREB) participated in cilostazol-induced HO-1 transcription. Furthermore, cilostazol triggered a linkage between the CRE and GT-repeat regions in the HO-1 promoter. The promoting effect of cilostazol on HO-1 expression, proliferation inhibition, and chromatin conformation in the HO-1 promoter was greater in VSMCs from subjects with shorter GT-repeat alleles than those with longer alleles.ConclusionsCilostazol inhibits VSMC proliferation involving an association between CREB and HO-1. The length polymorphism of GT-repeat in human HO-1 promoter determines the effect of cilostazol.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Cardiology - Volume 222, 1 November 2016, Pages 407-415
نویسندگان
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