Gene transfer of vascular endothelial growth factor reduces bleomycin-induced pulmonary hypertension in immature rabbits

Background: The purpose of the present paper was to investigate the effect of gene transfer of vascular endothelial growth factor (VEGF) on bleomycin (BLM)-induced pulmonary hypertension in immature rabbits. Methods: Immature rabbits (1 month old) were divided into control group (intratracheal injection of normal saline), BLM group (intratracheal injection of BLM), liposome group (intratracheal injection of BLM and liposomes) and the trans-gene group (intratracheal injection of BLM and DNA-liposome complex). The pulmonary arterial pressure (PAP) were measured by microcatheter, the pathological changes and the expression of VEGFmRNA and endothelial nitric oxide synthase (eNOS) mRNA of endothelial cells in pulmonary arteries were evaluated by hematoxylin-eosin (HE) and in situ hybridization. Results: The PAP of the BLM and liposome groups were higher than the PAP of the control and trans-gene groups. The thickness of wall increased and the cavity became narrow, and thickness index and area index increased in mid- and small-sized pulmonary arteries of the BLM and liposome groups. VEGF trans-gene was able to reduce those changes; the level of VEGFmRNA and eNOSmRNA expression in pulmonary arterial endothelial cells decreased in the BLM and liposome groups. The level of VEGFmRNA expression in the trans-gene group was higher than that in the BLM and liposome groups, but lower than that in the control group. Conclusion: The PAP was elevated, the thickness of wall increased and the cavity became narrow in mid- and small-sized pulmonary arteries, and the level of VEGFmRNA and eNOSmRNA expression in pulmonary arterial endothelial cells decreased in immature rabbits after 2 weeks of intratracheal injection of 4 units/kg BLM. VEGF trans-gene could reduce those changes.