Chronic hypoxia exacerbates pulmonary hypertension-induced right heart remodeling in mice by inhibiting GLS1-regulated glutaminolysis
10.3969/j.issn.1000-4718.2025.11.006
- VernacularTitle:慢性低氧通过抑制心肌GLS1调控的谷氨酰胺代谢加重肺动脉高压雄性小鼠右心重构
- Author:
Jinling HUANG
1
;
Ranran YAN
;
Guodan BAO
;
Zhenzhong BAI
Author Information
1. 青海大学附属医院呼吸与危重症医学科,青海 西宁 810001;青海大学医学院高原医学研究中心,青海 西宁 810001
- Publication Type:Journal Article
- Keywords:
pulmonary hypertension;
hypoxia;
glutamine;
right ventricular remodeling;
Hippo pathway
- From:
Chinese Journal of Pathophysiology
2025;41(11):2130-2136
- CountryChina
- Language:Chinese
-
Abstract:
AIM:This study aims to identify how glutamine metabolism affects pulmonary hypertension-in-duced right heart remodeling under chronic hypoxia.METHODS:C57BL/6J mice were randomly divided into control(n=10)and hypoxia(n=10)groups.The hypoxia group was exposed to a hypobaric chamber simulating an altitude of approxi-mately 5,500 m for 28 days.Right ventricular systolic pressure(RVSP)was measured by right heart catheterization.The right ventricle(RV),left ventricle,and interventricular septum(LV+S)were weighed,and the RV/(LV+S)ratio was cal-culated as an index of right ventricular hypertrophy.Metabolomics analysis using UPLC-Orbitrap mass spectrometry was performed on right ventricular tissues.Hematoxylin and eosin staining and immunofluorescence were used to detect YAP and GLS1 co-localization and expression intensity in the myocardium.Expression levels of Yes-associated protein(YAP),phosphorylated YAP(p-YAP),and glutaminase 1(GLS1)from the Hippo pathway were measured by Western blot in mouse right ventricular tissue.RESULTS:The RVSP and RVHI values,along with myocardial fiber sizes and volumes,were significantly increased in the hypoxia group compared to controls(P<0.01).Glutamine metabolism metabolites in right ventricular tissue were significantly decreased(P<0.01).Immunofluorescence revealed decreased GLS1 and in-creased YAP response intensity in the hypoxia group myocardium(P<0.01).Notably,p-YAP protein and GLS1 expres-sion decreased under hypoxic conditions(P<0.05 or P<0.01,respectively).CONCLUSION:Chronic hypoxia exacer-bates pulmonary hypertension-induced right heart remodeling by inhibiting glutaminolysis through glutaminase 1 via the Hippo pathway in mice.
