Abstract Objective To study the role of vascular endothelial growth factor-A (VEGF-A) in pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH) by regulating survivin (SVV). Methods A total of 96 neonatal rats were randomly divided into three groups: HPH+VEGF-A group, HPH group, and control group. Each group was further randomly divided into 3-, 7-, 10-, and 14-day subgroups (n=8 in each subgroup). The neonatal rats in the HPH+VEGF-A and HPH groups were intratracheally transfected with adenoviral vectors with or without VEGF-A gene respectively. Those in the control group were given intratracheal injection of normal saline and were then fed under normoxic conditions. The direct measurement method was used to measure mean right ventricular systolic pressure (RVSP). Hematoxylin-eosin staining was used to observe the morphological changes of pulmonary vessels under a light microscope and calculate the percentage of media wall thickness (MT%) and the percentage of media wall cross-sectional area (MA%) in the pulmonary arterioles. Immunohistochemistry was used to measure the expression levels of VEGF-A and SVV in lung tissue. Results The HPH group had a significantly higher mean RVSP than the control and HPH+VEGF-A groups at each time point (P < 0.05). Pulmonary vascular remodeling occurred in the HPH group on day 7 of hypoxia, while it occurred in the HPH+VEGF-A group on day 10 of hypoxia. On day 7 of hypoxia, the HPH group had significantly higher MT% and MA% than the control and HPH+VEGF-A groups (P < 0.05). On days 10 and 14 of hypoxia, the HPH and HPH+VEGF-A groups had significantly higher MT% and MA% than the control group (P < 0.05). The HPH and HPH+VEGF-A groups had significantly higher expression of VEGF-A than the control group at each time point (P < 0.05). On days 3 and 7 of hypoxia, the HPH+VEGF-A group had significantly higher expression of VEGF-A than the HPH group (P < 0.05). On day 14 of hypoxia, the HPH group had significantly higher expression of SVV than the control group (P < 0.05). The HPH+VEGF-A group had significantly higher expression of SVV than the control group at each time point (P < 0.05). On days 3 and 7 of hypoxia, the HPH+VEGF-A group had significantly higher expression of SVV than the HPH group (P < 0.05). Conclusions Prophylactic intratracheal administration of exogenous VEGF-A in neonatal rats with HPH can inhibit pulmonary vascular remodeling and reduce pulmonary arterial pressure by upregulating the expression of SVV in the early stage of hypoxia. This provides a basis for the interventional treatment of pulmonary vascular remodeling in neonatal HPH.
CAO Jing,LUO Jia-Yuan,WU Dian et al. Effect and mechanism of vascular endothelial growth factor-A on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension[J]. CJCP, 2021, 23(1): 103-110.
CAO Jing,LUO Jia-Yuan,WU Dian et al. Effect and mechanism of vascular endothelial growth factor-A on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension[J]. CJCP, 2021, 23(1): 103-110.
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