Abstract 12432: A Novel Vasculoprotective Role of Nitric Oxide Synthases in Bone Marrow-Derived Vascular Progenitor Cells
Background: Bone marrow-derived vascular progenitor cells in blood accumulate in injured arteries, differentiate into vascular wall cells, and contribute to arteriosclerotic vascular lesion formation. All three nitric oxide synthases (nNOS, eNOS, and iNOS) have been reported to be expressed in bone marrow cells. However, it remains to be clarified whether or not NOSs in bone marrow cells play a role in vascular lesion formation. We addressed this point in our triply n/i/eNOSs-deficient mice and in bone marrow transplantation experiments.
Methods and Results: Eight- to 12-week-old male wild-type (WT), triply NOSs-/-, and green fluorescent protein (GFP) transgenic mice were used. Vascular injury was induced by permanent ligation of unilateral carotid artery. Two weeks after carotid artery ligation, neointimal formation and constrictive vascular remodeling were noted in the ligated carotid arteries. In WT mice that underwent bone marrow transplantation from GFP transgenic mice, GFP-positive fluorescence was detected in the ligated carotid arteries, confirming the involvement of bone marrow-derived vascular progenitor cells in vascular lesion formation after carotid artery ligation. In NOSs-/- genotype that received WT bone marrow transplantation when compared with the same NOSs-/- genotype that received NOSs-/- bone marrow transplantation, the extent of neointimal formation and the extent of constrictive remodeling were both significantly less, along with significantly higher NOS activities in the ligated carotid arteries (each P≤0.05). Furthermore, in WT genotype with WT bone marrow transplantation when compared with the same WT genotype with NOSs-/- bone marrow transplantation, the extent of neointimal formation and the extent of constrictive remodeling were both significantly greater, associated with significantly lower NOS activities in the ligated carotid arteries (each P≤0.05).
Conclusions: These results indicate, for the first time, that NOSs in bone marrow cells exerts an inhibitory effect on vascular lesion formation caused by blood flow disruption in mice in vivo, demonstrating a novel vasculoprotective role of NOSs in bone marrow-derived vascular progenitor cells.
- © 2013 by American Heart Association, Inc.