Diverse Contribution of Bone Marrow–Derived Cells to Vascular Remodeling Associated With Pulmonary Arterial Hypertension and Arterial Neointimal Formation

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Abstract
Background— Recent evidence suggests that bone marrow (BM)–derived cells may differentiate into vascular cells that participate in arterial repair and/or lesion formation. However, it remains uncertain whether BM-derived cells also can participate in vascular remodeling associated with pulmonary arterial hypertension. Methods and Results— The BM of Sprague-Dawley rats was reconstituted with that of green fluorescent protein–transgenic rats. The BM-chimeric rats were injected intraperitoneally with 60 mg/kg monocrotaline after unilateral subpneumonectomy, and they concurrently underwent wire-mediated endovascular injury in femoral artery. After 28 days, they had elevated right ventricular systolic pressure (58.8±5.4 versus 20.4±2.4 mm Hg in sham-control; P<0.01). The pulmonary arterioles were markedly thickened, with an infiltration of green fluorescent protein–positive macrophages into the perivascular areas. The endothelium of pulmonary arterioles contained only a few green fluorescent protein–positive c...