文献类型：期刊文献

英文题名：Pulmonary Vascular Remodeling in Pulmonary Hypertension Mice Aggravated by Hypothyroidism

作者：Zhang, Hongling[1,2];Shao, Feifei[3];Gao, Cuixia[4];Tian, Limin[3]

第一作者：张惠玲;张虎林;Zhang, Hongling

通信作者：Tian, LM[1]

机构：[1]Gansu Univ Chinese Med, Lanzhou 730000, Gansu, Peoples R China;[2]Dingxi Second Peoples Hosp, Dept Resp, Dingxi 743000, Gansu, Peoples R China;[3]Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Endocrinol & Geriatr, Chengdu 610072, Peoples R China;[4]Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Hlth Management Ctr, Chengdu 610072, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, 32 Sect 2 West Yihuan Rd, Chengdu 610072, Peoples R China.

年份：2025

卷号：166

期号：9

外文期刊名：ENDOCRINOLOGY

收录：;Scopus(收录号：2-s2.0-105013329267);WOS:【SCI-EXPANDED(收录号:WOS:001549124300001)】；

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

语种：英文

外文关键词：hypothyroidism; pulmonary hypertension; pulmonary vascular remodeling; inflammation; oxidative stress

摘要：Objective This study aimed to investigate the impact of hypothyroidism on pulmonary vascular remodeling (PVR) in pulmonary hypertension (PH) mice and the therapeutic effects of levothyroxine (L-T4).Methods Male C57BL/6J mice were administered methimazole (MMI; 40 mg/kg/day) to induce hypothyroidism. PH was established using Sugen5416 combined with hypoxia (SuHx). Thyroid function was assessed by measuring serum free T4 (FT4) and TSH levels via ELISA. Echocardiography and hemodynamics were evaluated using the Vevo 3100 system and right heart catheterization. Pulmonary vascular morphology was analyzed by hematoxylin-eosin and Masson staining. Western blot and assay kits were used to assess inflammation, oxidative stress, and NF-kappa B pathway activation.Results SuHx-induced PH resulted in PVR, as evidenced by decreased pulmonary artery acceleration time (PAT) and PAT/pulmonary ejection time ratio, increased right ventricular (RV) systolic pressure, collagen deposition, and alpha-smooth muscle actin expression, along with RV dysfunction indicated by reduced tricuspid annular plane systolic excursion. MMI treatment for 4 weeks significantly lowered serum FT4 levels and increased TSH levels, inducing hypothyroidism. Compared to SuHx mice, SuHx + MMI mice exhibited exacerbated PH, RV dysfunction, and PVR, accompanied by increased levels of IL-1 beta, IL-6, TNF-alpha, and malondialdehyde; decreased glutathione levels and superoxide dismutase activity; and enhanced NF-kappa B pathway activation. L-T4 intervention attenuated these pathological changes.Conclusion Hypothyroidism exacerbates SuHx-induced PH by promoting PVR, inflammation, oxidative stress, and NF-kappa B pathway activation in mice. L-T4 supplementation alleviates these pathological changes. This study provides theoretical insights into the pathogenesis of hypothyroidism-related PH.