• Vascular Annual Meeting
• General Information
• Call for Abstracts
• Exhibitor Information
• Future Meeting Dates
• Past Meeting Information
• Contact Us

Increased Notch Pathway Expression During Vein Graft Adaptation In Young Adult But Not Aged Rats

Akihito Muto¹, Fabio A Kud^o1, Jose M Pimiento², Tamara N Fitzgerald¹, David Gortler¹, Toshiya Nishibe³, Alan Dardik.^1,4
1Yale University School of Medicine, New Haven, CT; ²Saint Mary's Hospital, Waterbury, CT; ³Fujita Health University Hospital, Toyoake, Japan; ⁴VA Connecticut Healthcare System, West Haven, CT.

OBJECTIVES: Successful vein graft adaptation to the arterial environment depends on VEGF signaling. Since most models of vein graft adaptation are performed in young animals, but vein grafts are commonly performed in elderly patients, we examined the effect of aging on vein graft adaptation and Notch expression, a family of genes downstream from VEGF whose expression is known to be regulated during aging.

METHODS: The jugular vein was placed as an interposition graft into the carotid artery of Fischer 344 male rats (6 and 24 month) and harvested after 3 weeks. Sections were stained by H&E and Masson’s Trichrome. mRNA expression was evaluated by qPCR and normalized by GAPDH.

RESULTS: Vein grafts showed thick neointima in aged but not young adult rats (p<0.01; n=7). Expression of the Notch ligand Dll4 was significantly increased in vein grafts placed in young adult rats (p=0.01; n=4) but not aged rats (p=0.59). The Notch-4 receptor showed significantly increased expression in young adult (p<0.01) but not aged rats. The Notch-3 receptor showed significantly decreased expression in young adult (p<0.01) but not aged rats. There was no difference in other Notch family ligands (Jagged-1 or -2) or Notch-1 receptor expression during vein graft adaptation. Expression of ephrin-B2, a determinant of arterial phenotype downstream of Notch, was increased in young adult but not aged rats (p=0.05).

CONCLUSIONS: Dll4, Notch-4 and Ephrin-B2 expression is increased, and Notch-3 is decreased during vein graft adaptation in young adult but not aged rats, coincident with lack of neointimal thickening in young adult rats. These results suggest that Notch pathway signaling may influence successful vein adaptation to the arterial environment, and impairment of Notch pathway signaling in aged patients may contribute in incomplete vein graft adaptation.