Zhou Xinming, Xiao Yongguang, Mao Zhifu, Huang Jie, Geng Qing, Wang Wei, Dong Ping
Department of Thoracic Surgery, People's Hospital of New District Longhua, Jianshedong Road, Longhua, Shenzhen, Guangzhou Province 518109, China.
Department of Thoracic Surgery, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuchang, Wuhan City, Hubei Province 430060, China.
Microvasc Res. 2015 Jul;100:9-16. doi: 10.1016/j.mvr.2015.01.009. Epub 2015 Feb 7.
The excessive proliferation of vascular smooth muscle cells was key factor in the restenosis of vein graft. And the Notch signaling was demonstrated to regulate vSMC proliferation and differentiation. Soluble Jagged-1 (sJag1) can inhibit Notch signaling in vitro and in vivo; however, its capacity to suppress restenosis of vein graft remains unknown. Under the microscope, the left jugular vein of these rats was interposed into the left common carotid artery, followed without any treatment (control), or with Ad-Jag1 (treatment) or placebo (DMSO) post operation. We showed that Ad-Jag1 can attenuate restenosis of vein graft by inducing decreased proliferation and increased apoptosis in vivo. Notch1-Hey2 signaling is critical for the development of intima thickening by controlling vSMC-fate determination. By blocking Notch signaling, Ad-Jag1 can significantly inhibit intima thickening. These studies identify that Ad-Jag1 can restore the vSMC phenotype and inhibit the vSMC proliferation by suppression of Notch1 signaling, and thus open a new avenue for the treatment of restenosis in vein graft.
血管平滑肌细胞的过度增殖是静脉移植物再狭窄的关键因素。并且已证明Notch信号通路可调节血管平滑肌细胞的增殖和分化。可溶性Jagged-1（sJag1）在体外和体内均可抑制Notch信号通路；然而，其抑制静脉移植物再狭窄的能力尚不清楚。在显微镜下，将这些大鼠的左颈静脉插入左颈总动脉，术后不进行任何处理（对照组），或给予Ad-Jag1（处理组）或安慰剂（二甲基亚砜）。我们发现Ad-Jag1可通过在体内诱导血管平滑肌细胞增殖减少和凋亡增加来减轻静脉移植物的再狭窄。Notch1-Hey2信号通路通过控制血管平滑肌细胞命运决定对内膜增厚的发展至关重要。通过阻断Notch信号通路，Ad-Jag1可显著抑制内膜增厚。这些研究表明，Ad-Jag1可通过抑制Notch1信号通路恢复血管平滑肌细胞表型并抑制血管平滑肌细胞增殖，从而为治疗静脉移植物再狭窄开辟了一条新途径。
