Nogo‐B limits intima‐media thickening during mouse vein graft adaptation

Abstract

Successful vein graft adaptation to the arterial environment is critical to maintain long‐term graft patency. However, the mechanism of vein graft adaptation remains unclear. Since Nogo‐B protects against vascular injury, we determined whether Nogo‐B plays a mechanistic role, limiting intima‐media thickening, during vein graft adaptation.Intrathoracic inferior vena cava was harvested from wild‐type (WT) or Nogo‐B knockout (Nogo‐KO) mice and placed as an interposition vein graft into the infrarenal aorta of WT mice. Vein grafts were harvested and analyzed after 2 or 3 weeks.In WT mouse vein grafts Eph‐B4 immunoreactivity decreased without increased Ephrin‐B2 immunoreactivity (n=4).Nogo‐KO vein grafts had increased intima‐media area compared to WT vein grafts (.25 mm2 vs .16 mm2, p<.05). However, Nogo‐KO vein grafts also had diminished Eph‐B4 immunoreactivity, similar to the decrease in WT vein grafts.Mouse vein grafts exhibit decreased markers of venous identity, recapitulating changes in humans and rats. Nogo‐KO vein grafts have loss of venous identity, similar to WT vein grafts, but increased intima‐media thickening. This data suggests that Nogo‐B plays a critical role during venous adaptation to an arterial environment independently of mechanisms that determine venous identity, and is also consistent with a general protective role of Nogo‐B in response to injury of the vasculature.