Soluble Jagged-1 inhibits neointima formation by attenuating Notch-Herp2 signaling.

Content Provider	Semantic Scholar
Author	Caolo, Vincenza Schulten, Henny M. Zhuang, Zhen W. Murakami, Masahiro Wagenaar, Allard Verbruggen, Sanne E. L. Molin, Daniël G. M. Post, M. Judith Donovan
Copyright Year	2011
Abstract	OBJECTIVE Notch has been implicated in neointima formation as reflected by increased Notch/Jagged expression on vascular injury and the promigratory effect of Notch signaling on smooth muscle cells. Soluble Jagged-1 (sJag1) has been shown to inhibit Notch signaling in vitro; however, its capacity to suppress neointima formation remains unknown. METHODS AND RESULTS Balloon injury of rat carotid arteries induced Notch1, Notch3, and Jagged-1 expression at days 3 and 14 postinjury. Notch signaling was activated as shown by increased expression of the Notch target gene Herp2. Adenoviral sJag1 (Ad-sJag1) transfection reduced neointima formation in carotid artery and enhanced reendothelialization, whereas adenoviral full-length Jagged-1 (Ad-Fl-Jag1) or LacZ had no effect. Injury-induced Herp2 expression was absent in vessels treated with Ad-sJag1. Consistently, Herp2 expression was reduced in Ad-sJag1-infected or recombinant sJag1 -treated coronary artery smooth muscle cells (CASMCs). Ad-sJag1 had no effect on human umbilical endothelial cell behavior, but it significantly reduced proliferation and migration of CASMCs. Overexpression of Herp2 in sJag1-treated CASMCs rescued the migratory and proliferative capacity in vitro. CONCLUSIONS Our results demonstrate that sJag1 can inhibit neointima formation after balloon injury by decreasing smooth muscle cell proliferation and migration through interference with Notch-Herp2 signaling.
Starting Page	258
Ending Page	262
Page Count	5
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://atvb.ahajournals.org/content/atvbaha/early/2011/02/17/ATVBAHA.110.217935.full.pdf?download=true
Alternate Webpage(s)	http://atvb.ahajournals.org/content/atvbaha/early/2011/02/17/ATVBAHA.110.217935.full.pdf
PubMed reference number	21330605v1
Alternate Webpage(s)	https://doi.org/10.1161/ATVBAHA.110.217935
DOI	10.1161/atvbaha.110.217935
Journal	Arteriosclerosis, thrombosis, and vascular biology
Volume Number	31
Issue Number	5
Language	English
Access Restriction	Open
Subject Keyword	Adenoviruses Artery Smooth Muscle Tissue Blood Vessel Carotid Arteries Jagged-1 Protein LacZ Genes Mumps virus soluble Ab:ACnc:Pt:Ser:Qn Muscle Cells Myocytes, Smooth Muscle NOTCH3 protein, human Neointima Recombinants Smooth muscle (tissue) Umbilicus (Anatomy) Vascular System Injuries alpha fetoprotein adenoviral vector vaccine
Content Type	Text
Resource Type	Article