文献类型：期刊文献

英文题名：TSH promotes right ventricle hypertrophy and energy metabolism remodeling in PAH mice

作者：Shao, Feifei[1,2];Zhang, Wenyan[2,3];Li, Xiaotao[2];Han, Ziqi[2,3];Lu, Xiao[2,3];Gao, Cuixia[4];Tian, Limin[1]

第一作者：Shao, Feifei

通信作者：Tian, LM[1]

机构：[1]Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Endocrinol & Geriatr, Chengdu, Peoples R China;[2]Gansu Prov Hosp, Dept Endocrinol, Lanzhou, Gansu, Peoples R China;[3]Gansu Univ Chinese Med, Sch Clin Med 1, Lanzhou, Peoples R China;[4]Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Hlth Management Ctr, Chengdu, Peoples R China

第一机构：Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Endocrinol & Geriatr, Chengdu, Peoples R China

通信机构：[1]corresponding author), Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Endocrinol & Geriatr, Chengdu, Peoples R China.

年份：2025

卷号：14

期号：11

外文期刊名：ENDOCRINE CONNECTIONS

收录：;Scopus(收录号：2-s2.0-105024193555);WOS:【SCI-EXPANDED(收录号:WOS:001631761800010)】；

基金：This study was supported by the National Natural Science Foundation of China(No. 82470829) and the Natural Science Foundation of Gansu Province(22JR5RA672).

语种：英文

外文关键词：thyroid-stimulating hormone, subclinical hypothyroidism, right ventricular; right ventricular hypertrophy; energy metabolism remodeling

摘要：Subclinical hypothyroidism is characterized by elevated thyroid stimulating hormone (TSH) levels and normal FT4, and is associated with an increased risk of cardiovascular diseases, but its specific impacts on the right ventricle and underlying mechanisms remain unclear. This study aimed to investigate the direct role of TSH signaling through its receptor in right ventricular hypertrophy and energy metabolism remodeling. A model of pulmonary arterial hypertension-induced right ventricular injury was created in male cardiomyocyte-specific TSH receptor knockout mice and control mice using Sugen5416 combined with hypoxia (10% O2). Cardiac function was assessed via echocardiography, while histological and molecular changes were examined through staining techniques, quantitative PCR, and Western blot. Metabolic alterations were quantified using ultra-high-performance liquid chromatography-tandem mass spectrometry. Results demonstrated that pulmonary hypertension induced right ventricular dysfunction, hypertrophy, and metabolic dysregulation in control mice, characterized by impaired systolic and diastolic function, increased glycolytic enzyme expression, lactate accumulation, and reduced ATP levels. These pathological changes were significantly attenuated in TSH receptor knockout mice. In vitro, TSH treatment promoted hypertrophic marker expression and shifted metabolic activity toward glycolysis in H9c2 cardiomyocytes. In conclusion, our in vivo and in vitro experiments demonstrate that TSH promotes cardiomyocyte hypertrophy and upregulates the glycolytic pathway. These findings reveal a direct contribution of elevated TSH to right ventricular injury and may offer novel mechanistic insights into right ventricular impairment associated with subclinical hypothyroidism.