Abstract：Objective To study the effect of platelet-derived growth factor-BB (PDGF-BB) on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH). Methods A total of 128 neonatal rats were randomly divided into four groups: PDGF-BB+HPH, HPH, PDGF-BB+normal oxygen, and normal oxygen (n=32 each). The rats in the PDGF-BB+HPH and PDGF-BB+normal oxygen groups were given an injection of 13 μL 6×1010 PFU/mL adenovirus with PDGF-BB gene via the caudal vein. After 24 hours of adenovirus transfection, the rats in the HPH and PDGF-BB+HPH groups were used to establish a neonatal rat model of HPH. Right ventricular systolic pressure (RVSP) was measured on days 3, 7, 14, and 21 of hypoxia. Hematoxylin-eosin staining was used to observe pulmonary vascular morphological changes under an optical microscope, and vascular remodeling parameters (MA% and MT%) were also measured. Immunohistochemistry was used to measure the expression levels of PDGF-BB and proliferating cell nuclear antigen (PCNA) in lung tissue. Results The rats in the PDGF-BB+HPH and HPH groups had a significantly higher RVSP than those of the same age in the normal oxygen group at each time point (P<0.05). The rats in the PDGF-BB+HPH group showed vascular remodeling on day 3 of hypoxia, while those in the HPH showed vascular remodeling on day 7 of hypoxia. On day 3 of hypoxia, the PDGF-BB+HPH group had significantly higher MA% and MT% than the HPH, PDGF-BB+normal oxygen, and normal oxygen groups (P<0.05). On days 7, 14, and 21 of hypoxia, the PDGF-BB+HPH and HPH groups had significantly higher MA% and MT% than the PDGF-BB+normal oxygen and normal oxygen groups (P<0.05). The PDGF-BB+HPH and HPH groups had significantly higher expression levels of PDGF-BB and PCNA than the normal oxygen group at all time points (P<0.05). On days 3, 7, and 14 of hypoxia, the PDGF-BB+HPH group had significantly higher expression levels of PDGF-BB and PCNA than the HPH group (P<0.05), while the PDGF-BB+normal oxygen group had significantly higher expression levels of PDGF-BB and PCNA than the normal oxygen group (P<0.05). Conclusions Exogenous administration of PDGF-BB in neonatal rats with HPH may upregulate the expression of PCNA, promote pulmonary vascular remodeling, and increase pulmonary artery pressure. Citation:Chinese Journal of Contemporary Pediatrics, 2023, 25(4): 407-414
GUO Xin,LI Ming-Xia,BAYER Caicike et al. Effect of platelet-derived growth factor-BB on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension and its mechanism[J]. CJCP, 2023, 25(4): 407-414.
1 Wang L, Li M. Roles of heat shock protein 70 toward hypoxia-induciblefactor 1α (HIF-1α) blockade in newborn rats withhypoxia-induced pulmonary hypertension[J]. Int J Clin Exp Med, 2018, 11(12): 13520-13527.
Wang L, Zheng Q, Yuan Y, et al. Effects of 17β-estradiol and 2-methoxyestradiol on the oxidative stress-hypoxia inducible factor-1 pathway in hypoxic pulmonary hypertensive rats[J]. Exp Ther Med, 2017, 13(5): 2537-2543. PMID: 28565876. PMCID: PMC5443199. DOI: 10.3892/etm.2017.4243.
Kikuchi N, Satoh K, Kurosawa R, et al. Selenoprotein P promotes the development of pulmonary arterial hypertension: possible novel therapeutic target[J]. Circulation, 2018, 138(6): 600-623. PMID: 29636330. DOI: 10.1161/CIRCULATIONAHA.117.033113.
Qian Z, Li Y, Yang H, et al. PDGFBB promotes proliferation and migration via regulating miR-1181/STAT3 axis in human pulmonary arterial smooth muscle cells[J]. Am J Physiol Lung Cell Mol Physiol, 2018, 315(6): L965-L976. PMID: 30211651. DOI: 10.1152/ajplung.00224.2018.
Li Y, Li L, Qian Z, et al. Phosphatidylinositol 3-kinase-DNA methyltransferase 1-miR-1281-histone deacetylase 4 regulatory axis mediates platelet-derived growth factor-induced proliferation and migration of pulmonary artery smooth muscle cells[J]. J Am Heart Assoc, 2018, 7(6): e007572. PMID: 29514810. PMCID: PMC5907547. DOI: 10.1161/JAHA.117.007572.
