title: Role of Jagged1 in arterial lesions after vascular injury.
abstract: OBJECTIVE
  Impaired regeneration of endothelial cells (EC) and overactivity of vascular smooth muscle cells (VSMC) are hallmarks of the arterial lesions associated with aging. The occurrence of 2 opposing cellular processes in the same arterial milieu makes pharmaceutical treatment difficult to develop. We previously reported that endothelial expression of a Notch ligand (Jagged1) was reduced in aged animals and that growth of the neointima was enhanced in these animals.
  
  
  RESULTS
  Similar to aged animals, Tie2-cre(+) Jagged1(lox/+) mice (with heterologous knockout of Jagged1 in EC) showed exaggerated intimal and medial thickening after carotid artery ligation. Unexpectedly, these mice showed little increase of Jagged1 expression not only in EC but also in VSMC, in contrast to a significant upregulation of Jagged1 in wild-type arteries after ligation. Coculture of VSMC with Jagged1-null EC resulted in the transition of VSMC from the contractile to the synthetic phenotype, along with decreased Jagged1 expression by VSMC. Conversely, overexpression of Jagged1 by EC or VSMC was shown to prevent the unfavorable phenotypic transition of VSMC, under both monoculture and coculture conditions.
  
  
  CONCLUSIONS
  These findings suggest a unidirectional effect of Jagged1 on both EC and VSMC that contributes to inhibition of arterial lesions after vascular injury. Our data also indicate that Jagged1 may be a novel therapeutic target for aging-related vascular diseases.
authors.affiliation: Cardiovascular Center of Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wu
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.forename: Hui
authors.initials: H
authors.lastname: Gong
authors.forename: Aijun
authors.initials: A
authors.lastname: Sun
authors.forename: Kaoru
authors.initials: K
authors.lastname: Tateno
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Katsube
authors.forename: Freddy
authors.initials: F
authors.lastname: Radtke
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
authors.forename: Tohru
authors.initials: T
authors.lastname: Minamino
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
mesh_terms: D000375:Aging / Q000473:pathology; D000818:Animals; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002339:Carotid Arteries / Q000473:pathology; D002450:Cell Communication; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D042787:Receptor, TIE-2; D000072099:Serrate-Jagged Proteins; D017539:Tunica Intima / Q000473:pathology; D057772:Vascular System Injuries / Q000473:pathology*
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D000072099:Serrate-Jagged Proteins; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; C079086:Tek protein, mouse