Soluble Jagged-1 Inhibits Neointima Formation by Attenuating Notch-Herp2 Signaling

Vincenza Caolo, Henny M. Schulten, Zhen W. Zhuang, Masahiro Murakami, Allard Wagenaar, Sanne Verbruggen, Daniel G. M. Molin, Mark J. Post*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

33 Citations (Web of Science)

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. Conclusion-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. (Arterioscler Thromb Vasc Biol. 2011;31:1059-1065.)
Original languageEnglish
Pages (from-to)1059-U270
JournalArteriosclerosis Thrombosis and Vascular Biology
Volume31
Issue number5
DOIs
Publication statusPublished - May 2011

Keywords

  • molecular biology
  • restenosis
  • vascular biology
  • neointima formation
  • Notch signaling

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