Prohibitin 2 Inhibits Right Ventricular Remodeling in Mice with Hypoxia-induced Pulmonary Hypertension
Objective:To explore the effects of prohibitin 2 on right ventricular remodeling in hypoxia-induced pulmonary hyper-tension(HPH)mice and potential mechanisms.Methods:Eight-week-old male mice were randomly allocated to the following 4 groups:control group,HPH group,HPH+vector group and HPH+PHB2 group.HPH group,HPH+vector group and HPH+PHB2 group were placed in low-pressure and low-oxygen artificial chamber,and control group were placed in atmospheric oxygen environment for 4 weeks.Adeno-associated virus serotype 9(AAV9)carrying smooth muscle promoter-driven SM22ap encoding PHB2 and empty vectors were injected via tail vein 3 weeks prior to model construction.Hemodynamics,the level of right ventricle remodeling,inflammation,ox-idative stress and vasoactive substances,and the expression levels of PHB2 and p-STAT3 were determined in mice.Results:Compared with control group,RVSP,RVAW,RVHI and CVP were increased significantly(P＜0.05)and RVID was decreased in HPH group and HPH+vector group(P＜0.05),with upregulated plasma ET-1 and BNP(P＜0.05)and downregulated NO,t-NOS and iNOS(P＜0.05),as well as increased IL-1β,IL-6 and TNF-α and decreased SOD and GSH-Px in right ventricular tissue(P＜0.05),and the levels ofPHB2 expres-sion in the lung tissue were decreased(P＜0.05)and p-STAT3 expression was increased(P＜0.05)in HPH group and HPH+vector group.Compared with HPH group and HPH+vector group,RVSP,RVAW,RVHI and CVP were decreased significantly(P＜0.05)and RVID was increased in HPH+PHB2 group(P＜0.05),with downregulated plasma ET-1 and BNP and upregulated NO,t-NOS and iNOS(P＜0.05),as well as decreased IL-1 β,IL-6 and TNF-α and increased SOD and GSH-Px in right ventricular tissue(P＜0.05),and the levels of PHB2 ex-pression in the lung tissue were increased(P＜0.05)and p-STAT3 expression was decreased(P＜0.05)in HPH+PHB2 group.Conclusion:PHB2 alleviates right ventricular remodeling in HPH mice,which may be related to the inhibition of STAT3 phosphorylation by PHB2 in pulmonary artery smooth muscle.
Prohibitin 2Hypoxia-induced pulmonary hypertensionVentricular remodelingSignal transduction and activator of transcription 3
NETL
NSTL
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