Abstract Objective To investigate the effect of heat shock protein 70(HSP70) on pulmonary arterial pressure and pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension(HPH).Methods A total of 128 Wistar neonatal rats were randomly divided into HPH model and blank control groups.According to the transfection solution, the HPH model group was further divided into normal saline group, empty virus group(viral vectors marked with a green fluorescent signal and not carrying the target gene), and virus+HSP70 group(viral vectors marked with a green fluorescent signal and carrying the target gene).The HPH model was established by inhalation of nitrogen-oxygen mixture(1.5 L/minutes and 8% oxygen).Pulmonary arterial pressure(mPAP) and the indicators of pulmonary vascular remodeling(MT% and MA%) were measured on days 3, 7, 10, and 14 of hypoxia.Results On days 3, 7, and 10 of hypoxia, the normal saline and empty virus groups had significantly enhanced expression of HSP70 compared with the blank control group(P<0.01), and the virus+HSP70 group had significantly higher expression of HSP70 than the blank control, normal saline, and empty virus groups(P<0.01).On day 14 of hypoxia, the expression of HSP70 showed no significant difference between these groups(P>0.05).On days 3, 7, and 10 of hypoxia, the normal saline and empty virus groups showed continuous increases in mPAP compared with the blank control group(P<0.05).There was no significant difference in mPAP between the virus+HSP70 and blank control groups(P>0.05).On day 14 of hypoxia, there was no significant difference in mPAP among three subgroups of the HPH model group(P>0.05), but the mPAP in the three subgroups was significantly higher than in the blank control group(P<0.05).After 7 days of hypoxia, the normal saline and empty virus groups showed significantly higher MT% and MA% than the blank control group(P<0.05), but the two indicators showed no significant differences between the virus+HSP70 and the blank control groups(P>0.05).On day 14 of hypoxia, there were no significant differences in MT% and MA% among three subgroups of the HPH model group(P>0.05), but the MT% and MA% in the three subgroups were higher than in the blank control group(P<0.05).Conclusions HSP70 may reduce pulmonary arterial pressure and pulmonary vascular remodeling in neonatal rats with HPH.
LIU Kun-Zhen,WANG Le,LI Ming-Xia. Effect of heat shock protein 70 on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension[J]. CJCP, 2016, 18(2): 152-158.
LIU Kun-Zhen,WANG Le,LI Ming-Xia. Effect of heat shock protein 70 on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension[J]. CJCP, 2016, 18(2): 152-158.
Luo W, Zhong J, Chong R, et al. Hsp70 and CHIP selectively mediate ubiquitination and degradation of hypoxia-inducible factor(HIF)-1alpha but not HIF-2alpha[J]. J Biol Chem, 2010, 285(6):3651-3663.
[3]
van de Sluis B, Groot AJ, Vermeulen J, et al. COMMD1 promotes pVHL and O2-independent proteolysis of HIF-1alpha via HSP90/70[J]. PLoS One, 2009, 4(10):e7332.
Wang L, Zhou Y, Li M, et al. Expression of hypoxia-inducible factor-1α, endothelin-1 and adrenomedulin in newborn rats with hypoxia-induced pulmonary hypertension[J]. Exp Ther Med, 2014, 8(1):335-339.
Gogate SS, Fujita N, Skubutyte R, et al. Tonicity enhancer binding protein(TonEBP) and hypoxia-inducible factor(HIF) coordinate heat shock protein 70(Hsp70) expression in hypoxic nucleus pulposus cells:role of Hsp70 in HIF-1α degradation[J]. J Bone Miner Res, 2012, 27(5):1106-1117.
