{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:19:40Z","timestamp":1792700380142,"version":"4.5.0"},"reference-count":48,"publisher":"The Endocrine Society","issue":"9","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 82470829"],"award-info":[{"award-number":["No. 82470829"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004775","name":"Natural Science Foundation of Gansu Province","doi-asserted-by":"publisher","award":["22JR5RA672"],"award-info":[{"award-number":["22JR5RA672"]}],"id":[{"id":"10.13039\/501100004775","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>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).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Male C57BL\/6J mice were administered methimazole (MMI; 40\u2005mg\/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-\u03baB pathway activation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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 \u03b1-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\u03b2, IL-6, TNF-\u03b1, and malondialdehyde; decreased glutathione levels and superoxide dismutase activity; and enhanced NF-\u03baB pathway activation. L-T4 intervention attenuated these pathological changes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Hypothyroidism exacerbates SuHx-induced PH by promoting PVR, inflammation, oxidative stress, and NF-\u03baB pathway activation in mice. L-T4 supplementation alleviates these pathological changes. This study provides theoretical insights into the pathogenesis of hypothyroidism-related PH.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/endocr\/bqaf122","type":"journal-article","created":{"date-parts":[[2025,8,10]],"date-time":"2025-08-10T11:41:38Z","timestamp":1754826098000},"source":"Crossref","is-referenced-by-count":1,"title":["Pulmonary Vascular Remodeling in Pulmonary Hypertension Mice Aggravated by Hypothyroidism"],"prefix":"10.1210","volume":"166","author":[{"given":"Hongling","family":"Zhang","sequence":"first","affiliation":[{"name":"Gansu University of Chinese Medicine , Lanzhou, Gansu 730000 ,","place":["China"]},{"name":"Department of Respiratory, Dingxi Second People's Hospital , Dingxi, Gansu 743000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8799-0806","authenticated-orcid":false,"given":"Feifei","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Geriatrics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China , Chengdu 610072 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuixia","family":"Gao","sequence":"additional","affiliation":[{"name":"Health Management Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China , Chengdu 610072 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4769-4375","authenticated-orcid":false,"given":"Limin","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Geriatrics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China , Chengdu 610072 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"issue":"1","key":"2025081221090087500_bqaf122-B1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/eurheartj\/ehv317","article-title":"2015 ESC\/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT)","volume":"37","author":"Gali\u00e8","year":"2016","journal-title":"Eur Heart J"},{"issue":"1","key":"2025081221090087500_bqaf122-B2","doi-asserted-by":"crossref","first-page":"1801913","DOI":"10.1183\/13993003.01913-2018","article-title":"Haemodynamic definitions and updated clinical classification of pulmonary hypertension","volume":"53","author":"Simonneau","year":"2019","journal-title":"Eur Respir J"},{"issue":"5","key":"2025081221090087500_bqaf122-B3","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S0002-9629(15)40640-8","article-title":"High prevalence of hypothyroidism in patients with primary pulmonary hypertension","volume":"318","author":"Curnock","year":"1999","journal-title":"Am J Med Sci"},{"issue":"1","key":"2025081221090087500_bqaf122-B4","first-page":"10","article-title":"Frequency of hypothyroidism among patients of pulmonary hypertension","volume":"30","author":"Sami","year":"2023","journal-title":"Prof Med J"},{"issue":"3","key":"2025081221090087500_bqaf122-B5","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1378\/chest.07-0366","article-title":"Pulmonary hypertension and thyroid disease","volume":"132","author":"Li","year":"2007","journal-title":"Chest"},{"issue":"5","key":"2025081221090087500_bqaf122-B6","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.amjmed.2003.09.040","article-title":"Hypothyroidism and pulmonary arterial hypertension","volume":"116","author":"Ghamra","year":"2004","journal-title":"Am J Med"},{"issue":"18","key":"2025081221090087500_bqaf122-B7","first-page":"695","article-title":"Thyroid dysfunction in patients with pulmonary arterial hypertension. 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