title: Soluble Jagged-1 inhibits neointima formation by attenuating Notch-Herp2 signaling.
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.
  
  
  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.
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, the Netherlands.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Caolo
authors.forename: Henny M
authors.initials: HM
authors.lastname: Schulten
authors.forename: Zhen W
authors.initials: ZW
authors.lastname: Zhuang
authors.forename: Masahiro
authors.initials: M
authors.lastname: Murakami
authors.forename: Allard
authors.initials: A
authors.lastname: Wagenaar
authors.forename: Sanne
authors.initials: S
authors.lastname: Verbruggen
authors.forename: Daniel G M
authors.initials: DG
authors.lastname: Molin
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Post
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002339:Carotid Arteries / Q000378:metabolism* / Q000473:pathology; D020212:Carotid Artery Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D006965:Hyperplasia; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051881:Receptor, Notch1 / Q000378:metabolism*; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D017539:Tunica Intima / Q000378:metabolism* / Q000473:pathology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051881:Receptor, Notch1; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D012097:Repressor Proteins; D000072099:Serrate-Jagged Proteins; C082692:Hes2 protein, rat; C000606273:JAG1 protein, human; C000606275:Jag1 protein, rat; C497763:Notch1 protein, rat; C498556:Notch3 protein, rat