Hemodynamic
pulmonary arterial hypertension (
HPAH) is a common symptom in
congenital heart disease (CHD) patients with a left-to-right shunt. Endothelial
NO synthase (eNOS) and endothelial-like progenitor cells result in significant improvement of right ventricular systolic pressure in established
pulmonary arterial hypertension (PAH) models. We hypothesized that bone marrow (BM)-derived endothelial progenitor cells (EPCs) and eNOS would prevent
HPAH in a newly established rat model. The heNOS gene was cloned into a PSUCMV vector, and a high-titer adenovirus was generated. Mononuclear cells (MNCs) from rat BM were differentiated into EPCs by treatment with various
cytokines, and a high purity of EPCs (>70%) was confirmed using the markers DiI ac-
LDL, UEA-1, vWF and Flk-1. An ideal rat
HPAH model was successfully established based on right lung lobectomy, and was confirmed by pressure measurement and histological staining. heNOS was successfully transfected into EPCs, which were then transplanted into
HPAH rats. Two weeks after
transplantation, the systolic pulmonary arterial blood pressure (sPAP) was significantly reduced by heNOS-EPCs treatment and by
transplantation of control EPCs. The high number of muscular pulmonary arteries and the thickness of the muscular coat characteristic of
HPAH rats were clearly reversed or even restored to normal levels following
transplantation of EPCs, particularly eNOS-EPCs. These findings indicate a critical role of eNOS in
HPAH treatment and suggest that eNOS-transfected EPCs may provide an effective strategy for
HPAH treatment in CHD patients.