Alcohol inhibits smooth muscle cell proliferation via regulation of the Notch signaling pathway.
Alcohol inhibits smooth muscle cell proliferation via regulation of the Notch signaling pathway.
复制标题
DOI：
10.1161/atvbaha.110.215681
复制
发表时间：
2010-12
期刊：
影响因子：
--
通讯作者：
Redmond EM
中科院分区：
文献类型：
--
作者：
Morrow D;Cullen JP;Liu W;Cahill PA;Redmond EM
探讨Notch信号通路在酒精抑制平滑肌细胞（SMC）增殖中的作用。用乙醇（EtOH）处理人冠状动脉SMCs可降低Notch 1 mRNA和Notch 1胞内结构域蛋白水平，但对Notch 3无任何影响。EtOH处理还降低了c -启动子结合因子-1 (CBF-1)/重组信号结合蛋白(RBP)-jk启动子活性和Notch靶基因（毛相关转录因子[HRT-1]或HRT-2）的表达。这些作用与EtOH对SMC增殖的抑制作用同时存在。过表达构成活性的Notch 1胞内结构域或人毛相关转录因子-1 （hHRT-1）可阻止etoh诱导的SMC增殖抑制。在体内，结扎诱导颈动脉重构后Notch 1和HRT-1 mRNA表达升高。在每天灌胃“适量”酒精的小鼠中，血管重塑反应被抑制；内膜-内膜增厚明显减少，内膜和新内膜SMC增殖细胞核抗原表达降低。此外，适量饮酒可抑制结扎损伤后诱导的Notch 1和HRT-1表达。在体外和体内，EtOH抑制Notch信号传导，随后抑制SMC增殖。EtOH对SMCs中Notch信号的调节可能与流行病学研究表明的适度饮酒对心血管的保护作用有关。
To determine the role of Notch signaling in mediating alcohol’s inhibition of smooth muscle cell (SMC) proliferation. Treatment of human coronary artery SMCs with ethanol (EtOH) decreased Notch 1 mRNA and Notch 1 intracellular domain protein levels, in the absence of any effect on Notch 3. EtOH treatment also decreased C-promoter binding factor-1 (CBF-1)/recombination signal-binding protein (RBP)-jk promoter activity and Notch target gene (hairy related transcription factor [HRT-1] or HRT-2) expression. These effects were concomitant with an inhibitory effect of EtOH on SMC proliferation. Overexpression of constitutively active Notch 1 intracellular domain or human hairy related transcription factor-1 (hHRT-1) prevented the EtOH-induced inhibition of SMC proliferation. In vivo, Notch 1 and HRT-1 mRNA expression was increased after ligation-induced carotid artery remodeling. The vessel remodeling response was inhibited in mice that received “moderate” amounts of alcohol by gavage daily; intimal-medial thickening was markedly reduced, and medial and neointimal SMC proliferating cell nuclear antigen expression was decreased. Moreover, Notch 1 and HRT-1 expression, induced after ligation injury, was inhibited by moderate alcohol consumption. EtOH inhibits Notch signaling and, subsequently, SMC proliferation, in vitro and in vivo. The modulation of Notch signaling in SMCs by EtOH may be relevant to the cardiovascular protective effects of moderate alcohol consumption purported by epidemiological studies.