title: Soluble Jagged-1 inhibits restenosis of vein graft by attenuating Notch signaling.
abstract: 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.
authors: Department of Thoracic Surgery, People's Hospital of New District Longhua, Jianshedong Road, Longhua, Shenzhen, Guangzhou Province 518109, China. Electronic address: zhouxm0101@163.com.
authors: Xinming
authors: X
authors: Zhou
authors: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuchang, Wuhan City, Hubei Province 430060, China. Electronic address: yongguangxiao@gmail.com.
authors: Yongguang
authors: Y
authors: Xiao
authors: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuchang, Wuhan City, Hubei Province 430060, China. Electronic address: Chest-mzf@163.com.
authors: Zhifu
authors: Z
authors: Mao
authors: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuchang, Wuhan City, Hubei Province 430060, China. Electronic address: doctor_huangjie@126.com.
authors: Jie
authors: J
authors: Huang
authors: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuchang, Wuhan City, Hubei Province 430060, China. Electronic address: szgqing@126.com.
authors: Qing
authors: Q
authors: Geng
authors: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuchang, Wuhan City, Hubei Province 430060, China. Electronic address: wangwei1018@yeah.net.
authors: Wei
authors: W
authors: Wang
authors: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuchang, Wuhan City, Hubei Province 430060, China. Electronic address: dodo3753@163.com.
authors: Ping
authors: P
authors: Dong
mesh_terms: D000818:Animals; D017209:Apoptosis; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D017536:Carotid Artery, Common / Q000601:surgery; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D006083:Graft Occlusion, Vascular / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D000072100:Jagged-1 Protein; D007601:Jugular Veins / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D058426:Neointima; D010641:Phenotype; D017208:Rats, Wistar; D051881:Receptor, Notch1 / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D058017:Vascular Grafting
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606275:Jag1 protein, rat; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497763:Notch1 protein, rat; D051881:Receptor, Notch1; D000072099:Serrate-Jagged Proteins
keywords: Intimal hyperplasia; Phenotype; Smooth muscle cells; Soluble Jagged-1; Vein graft