The Preliminary Experimental Study On HGF/c-Met-mediated Endothelial Progenitor Cells (EPCs) Transplanted Into Hypoxic Pulmonaryartery Hypertension Rats

Objective: To investigate the effect of HGF/c-Met-mediated endothelial progenitor cells(EPCs)transplanted into hypoxic pulmonary artery hypertension rats.Methods: Induction of HPAH model in rats;cultivation and in vitro identification of primary EPCs;construction of recombinant adenovirus plasmid carring c-Met gene and stable transfected EPCs.The rats were divided into four groups: c-Met-EPCs group,EPCs group,pulmonary hypertension group and normal control.The first two groups were transfused with c-Met-EPCs and EPCs via tail vein,respectively.The latter two groups were transfused with normal saline(NS)via tail vein,respectively.After normal feeding a week,meanpulmonary artery pressure(mPAP)and right ventricle hypertrophy index(RVHI)were determined.Ultrastructural pathology observation of pulmonary artery was determined by transmission electron microscope.Histopathological sections of the lung tissues of the rats were stained by HE stain for the observation ofhistopathological changes.ELISA for the determination of content of endothelin-1(ET-1)in serum.Griess method for the determination of content of nitric oxide(NO)in serum.Results: The measured values of mPAP among four groups were(23.17±3.07),(30.85±3.15),(33.55±5.47),(20.30±1.99)mmHg,respectively.The measured values of RVHI among four groups were(32.48±2.38)%,(37.54±4.42)%,(38.53±2.81)%,(26.05±3.05)%,respectively.The content of ET-1 among four groups were(69.45±6.32),(95.76±7.31),(99.14±8.39),(62.35±6.06)ng/L,respectively.The content of NO among four groups were(99.63±11.40),(56.07±3.32),(48.83±6.56),(125.50±12.26)?mol/L,respectively.The measured values of mPAP,RVHI and content of ET-1 in EPCs group and pulmonary hypertension group were significantly higher than normal control(P<0.05).Meanwhile,the measured values of above-mentioned indexes in c-Met-EPCs group were significantly lower than EPCs group and pulmonary hypertension group(P<0.05).The measured value of NO in EPCs group and pulmonary hypertension group was significantly lower than normal control(P<0.05).And the measured values of NO in c-Met-EPCs group was significantly higher than EPCs group and pulmonary hypertension group(P<0.05).Transmission electron microscope showed obvious swelling and extension of mitochondrion and endoplasmic reticulum in pulmonary artery endothelial cells and medial smooth muscle cells and discontinuousdistribution of endothelial cells in EPCs group and pulmonary hypertension group.Correspondingly,there were no significance above-mentioned changes in c-Met-EPCs group.Lung tissue pathological section showed that there was significance pulmonary vascular remodeling in EPCs group and pulmonary hypertension group;however,this was dramatically suppressed in c-Met-EPCs group.Conclusion: HGF/c-Met-mediated EPCs can decrease pulmonary vascular resistance and improve pulmonary vascular remodeling in hypoxic pulmonary hypertension rats.The mechanism of effect of its may be related to the inhibition of ET-1 and promotion of NO production.