[Effect of VEGF gene transfer on the bleomycin-induced pulmonary hypertension in immature rabbits].
To investigate the effect of vascular endothelial growth factor (VEGF) gene transfer on the bleomycin(BLM)-induced pulmonary hypertension in immature rabbits.



Immature rabbits were divided into 4 groups; control, BLM, liposome and trans-gene groups. The systolic, diastolic and mean pulmonary artery pressure (PASP, PADP, MPAP) were measured by micro-catheter, the pathological changes and the expression of VEGFmRNA and eNOSmRNA of endothelial cells in pulmonary arteries were evaluated by HE stain and in situ hybridization.



(1) The PAP of BLM and liposome groups was higher than that of control and trans-gene groups. The PASP was 16.5+/-2.9, 25.2+/-7.0, 24.4+/-6.0 and 18.3+/-2.7 mmHg; the PADP was 8.8+/-4.2, 13.1+/-3.8, 13.7+/-4.6 and 10.2+/-2.6 mmHg; the MPAP was 12.1+/-4.0, 18.4+/-4.7, 18.4+/-5.1 and 14.1+/-2.5 mmHg in control, BLM, liposome and trans-gene groups respectively. (2) The thickness of wall increased and the cavity became narrow, and the thickness index (TI) and area index (AI) increased in middle and small pulmonary arteries of BLM and liposome groups. The TI was 0.52+/-0.16, 0.65+/-0.16, 0.63+/-0.11 and 0.55+/-0.13; and the AI was 0.74+/-0.17, 0.84+/-0.14, 0.85+/-0.08 and 0.79+/-0.12 in control, BLM, liposome and trans-gene groups,respectively. (3) The level of VEGFmRNA and eNOSmRNA expression in pulmonary arterial endothelial cells decreased in BLM and liposome groups. The level of VEGFmRNA and eNOSmRNA expression in trans-gene group was higher than that in BLM and liposome groups, but lower than that in control group. VEGFmRNA was 0.83+/-0.09, 0.45+/-0.11, 0.45+/-0.13 and 0.65+/-0.18; eNOSmRNA was 0.79+/-0.12, 0.45+/-0.12, 0.50+/-0.14 and 0.56+/-0.08 in control, BLM, liposome and trans-gene groups, respectively.



VEGF gene transfer in immature rabbits with BLM-induced pulmonary hypertension could attenuate the increasing of PAP and wall thickness in middle and small pulmonary arteries, and increase the level of VEGFmRNA and eNOSmRNA expression in pulmonary arterial endothelial cells.
Gong
Fang-qi
FQ
The Children's Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China. gongfangqi@zju.edu.cn
Tang
Hong-feng
HF
Lin
You-min
YM
Gu
Wei-zhong
WZ
Wang
Wei
W
Kang
Man-li
ML
D000818:Animals; D000831:Animals, Newborn; D001761:Bleomycin; D004727:Endothelium / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis* / Q000235:genetics; D011651:Pulmonary Artery / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011817:Rabbits; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics*
D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D001761:Bleomycin; D052250:Nitric Oxide Synthase Type III