{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T02:39:38Z","timestamp":1782441578528,"version":"3.54.5"},"reference-count":26,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The expression status of proinflammatory cytokines in high-altitude pulmonary arterial hypertension (PAH) has been well studied. However, the changes in interleukin (IL)-8 and tumor necrosis factor \u03b1 (TNF-\u03b1) during the reversible changes in pulmonary vascular remodeling (PVR) in PAH after detaching from a hypobaric hypoxic environment have not been elucidated. This investigation elucidated a high-altitude PAH rat model. Then, PAH rats in the high-altitude group were maintained in the high-altitude area, and rats in the low-altitude group returned to the low-altitude area. After 0, 10, 20, and 30 days of PAH modeling, right ventricular systolic pressure (RVSP) and the mean pulmonary arterial pressure (mPAP) were assessed. Right ventricular (RV) hypertrophy was reflected by the ratio of RV\/[left ventricle + interventricular septum (S)]. Pathological changes in PVR were accessed by hematoxylin-eosin staining, and medial wall thickness (WT%) and medial wall area (WA%) were measured. TNF-\u03b1 and IL-8 levels in pulmonary artery tissues and blood were measured with Western blot assay and enzyme-linked immunosorbent assay, respectively. Our results showed that PAH rats exhibited a substantial increase in RVSP and mPAP, RV hypertrophy, PVR, and enhanced generation of TNF-\u03b1 and IL-8. Then, we found that these pathological changes were gradually aggravated and TNF-\u03b1 and IL-8 levels were increased in rats in the high-altitude group after 10, 20, and 30 days of PAH modeling. In contrast, the mPAP was decreased and PVR was alleviated in rats in the low-altitude group, accompanying with reduced TNF-\u03b1 and IL-8 production. In conclusion, our study demonstrated that the generation of TNF-\u03b1 and IL-8 was also reversible during the reversible changes in PVR after detaching from a hypobaric hypoxic environment. Thus, proinflammatory cytokine TNF-\u03b1 and IL-8 levels are positively correlated with PVR severity.<\/jats:p>","DOI":"10.1515\/biol-2022-0650","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T15:51:24Z","timestamp":1690473084000},"source":"Crossref","is-referenced-by-count":7,"title":["TNF-\u03b1 and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats"],"prefix":"10.1515","volume":"18","author":[{"given":"Haixia","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Emergency, Affiliated Hospital of Qinghai University , Xining City , Qinghai Province 810001 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongfeng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Emergency, Affiliated Hospital of Qinghai University , Xining City , Qinghai Province 810001 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency, Affiliated Hospital of Qinghai University , Xining City , Qinghai Province 810001 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Emergency, Affiliated Hospital of Qinghai University , Xining City , Qinghai Province 810001 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dehua","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Emergency, Affiliated Hospital of Qinghai University , Xining City , Qinghai Province 810001 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenchen","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Emergency, Affiliated Hospital of Qinghai University , Xining City , Qinghai Province 810001 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2023,7,27]]},"reference":[{"key":"2023090109413389060_j_biol-2022-0650_ref_001","doi-asserted-by":"crossref","unstructured":"Luna-L\u00f3pez R, Ruiz Mart\u00edn A, Escribano Sub\u00edas P. Pulmonary arterial hypertension. Med Clin (Barc). 2022;158(12):622\u20139.","DOI":"10.1016\/j.medcle.2022.05.010"},{"key":"2023090109413389060_j_biol-2022-0650_ref_002","doi-asserted-by":"crossref","unstructured":"Rajagopal S, Yu YA. The Pathobiology of Pulmonary Arterial Hypertension. Cardiol Clin. 2022;40(1):1\u201312.","DOI":"10.1016\/j.ccl.2021.08.001"},{"key":"2023090109413389060_j_biol-2022-0650_ref_003","doi-asserted-by":"crossref","unstructured":"Hu L, Zhao C, Chen Z, Hu G, Li X, Li Q. An emerging strategy for targeted therapy of pulmonary arterial hypertension: Vasodilation plus vascular remodeling inhibition. Drug Discov Today. 2022;27(5):1457\u201363.","DOI":"10.1016\/j.drudis.2022.01.011"},{"key":"2023090109413389060_j_biol-2022-0650_ref_004","doi-asserted-by":"crossref","unstructured":"Gomes MT, Bai Y, Potje SR, Zhang L, Lockett AD, Machado RF. Signal transduction during metabolic and inflammatory reprogramming in pulmonary vascular remodeling. Int J Mol Sci. 2022;23(5):2410.","DOI":"10.3390\/ijms23052410"},{"key":"2023090109413389060_j_biol-2022-0650_ref_005","doi-asserted-by":"crossref","unstructured":"Kenny M, Clarke MM, Pogue KT. Overview of riociguat and its role in the treatment of pulmonary hypertension. J Pharm Pract. 2022;35(3):437\u201344.","DOI":"10.1177\/0897190020961291"},{"key":"2023090109413389060_j_biol-2022-0650_ref_006","doi-asserted-by":"crossref","unstructured":"Sydykov A, Mamazhakypov A, Maripov A, Kosanovic D, Weissmann N, Ghofrani HA, et al. Pulmonary hypertension in acute and chronic high altitude maladaptation disorders. Int J Environ Res Public Health. 2021;18(4):1692.","DOI":"10.3390\/ijerph18041692"},{"key":"2023090109413389060_j_biol-2022-0650_ref_007","doi-asserted-by":"crossref","unstructured":"Brakema EA, Tabyshova A, Kasteleyn MJ, Molendijk E, van der Kleij R, van Boven JFM, et al. High COPD prevalence at high altitude: does household air pollution play a role? Eur Respir J. 2019;53(2):1801193.","DOI":"10.1183\/13993003.01193-2018"},{"key":"2023090109413389060_j_biol-2022-0650_ref_008","doi-asserted-by":"crossref","unstructured":"Hu Y, Chi L, Kuebler WM, Goldenberg NM. Perivascular inflammation in pulmonary arterial hypertension. Cells. 2020;9(11):2338.","DOI":"10.3390\/cells9112338"},{"key":"2023090109413389060_j_biol-2022-0650_ref_009","doi-asserted-by":"crossref","unstructured":"Sakuma M, Toyoda S, Inoue T, Node K. Inflammation in pulmonary artery hypertension. Vascul Pharmacol. 2019;118\u2013119:106562.","DOI":"10.1016\/j.vph.2019.05.002"},{"key":"2023090109413389060_j_biol-2022-0650_ref_010","doi-asserted-by":"crossref","unstructured":"Frid MG, Thurman JM, Hansen KC, Maron BA, Stenmark KR. Inflammation, immunity, and vascular remodeling in pulmonary hypertension; Evidence for complement involvement? Glob Cardiol Sci Pract. 2020;2020(1):e202001.","DOI":"10.21542\/gcsp.2020.1"},{"key":"2023090109413389060_j_biol-2022-0650_ref_011","doi-asserted-by":"crossref","unstructured":"Matsushima K, Yang D, Oppenheim JJ. Interleukin-8: An evolving chemokine. Cytokine. 2022;153:155828.","DOI":"10.1016\/j.cyto.2022.155828"},{"key":"2023090109413389060_j_biol-2022-0650_ref_012","doi-asserted-by":"crossref","unstructured":"Lin RL, Gu Q, Khosravi M, Lee LY. Sustained sensitizing effects of tumor necrosis factor alpha on sensory nerves in lung and airways. Pulm Pharmacol Ther. 2017;47:29\u201337.","DOI":"10.1016\/j.pupt.2017.06.001"},{"key":"2023090109413389060_j_biol-2022-0650_ref_013","doi-asserted-by":"crossref","unstructured":"Jang DI, Lee AH, Shin HY, Song HR, Park JH, Kang TB, et al. The role of tumor necrosis factor alpha (tnf-\u03b1) in autoimmune disease and current tnf-\u03b1 inhibitors in therapeutics. Int J Mol Sci. 2021;22(5):2719.","DOI":"10.3390\/ijms22052719"},{"key":"2023090109413389060_j_biol-2022-0650_ref_014","doi-asserted-by":"crossref","unstructured":"Yang Z, Sun H, Su S, Nan X, Li K, Jin X, et al. Tsantan sumtang restored right ventricular function in chronic hypoxia-induced pulmonary hypertension rats. Front Pharmacol. 2020;11:607384.","DOI":"10.3389\/fphar.2020.607384"},{"key":"2023090109413389060_j_biol-2022-0650_ref_015","doi-asserted-by":"crossref","unstructured":"Ishikawa T, Abe K, Takana-Ishikawa M, Yoshida K, Watanabe T, Imakiire S, et al. Chronic inhibition of toll-like receptor 9 ameliorates pulmonary hypertension in rats. J Am Heart Assoc. 2021;10(7):e019247.","DOI":"10.1161\/JAHA.120.019247"},{"key":"2023090109413389060_j_biol-2022-0650_ref_016","doi-asserted-by":"crossref","unstructured":"Kabwe JC, Sawada H, Mitani Y, Oshita H, Tsuboya N, Zhang E, et al. CRISPR-mediated Bmpr2 point mutation exacerbates late pulmonary vasculopathy and reduces survival in rats with experimental pulmonary hypertension. Respir Res. 2022;23(1):87.","DOI":"10.1186\/s12931-022-02005-w"},{"key":"2023090109413389060_j_biol-2022-0650_ref_017","doi-asserted-by":"crossref","unstructured":"Chai T, Qiu C, Xian Z, Lu Y, Zeng Y, Li J. A narrative review of research advances in hypoxic pulmonary hypertension. Ann Transl Med. 2022;10(4):230.","DOI":"10.21037\/atm-22-259"},{"key":"2023090109413389060_j_biol-2022-0650_ref_018","doi-asserted-by":"crossref","unstructured":"Kylhammar D, Hesselstrand R, Nielsen S, Scheele C, R\u00e5degran G. Angiogenic and inflammatory biomarkers for screening and follow-up in patients with pulmonary arterial hypertension. Scand J Rheumatol. 2018;47(4):319\u201324.","DOI":"10.1080\/03009742.2017.1378714"},{"key":"2023090109413389060_j_biol-2022-0650_ref_019","doi-asserted-by":"crossref","unstructured":"Liu J, Cai G, Li M, Fan S, Yao B, Ping W, et al. Fibroblast growth factor 21 attenuates hypoxia-induced pulmonary hypertension by upregulating PPAR\u03b3 expression and suppressing inflammatory cytokine levels. Biochem Biophys Res Commun. 2018;504(2):478\u201384.","DOI":"10.1016\/j.bbrc.2018.09.004"},{"key":"2023090109413389060_j_biol-2022-0650_ref_020","doi-asserted-by":"crossref","unstructured":"Shu J, Liu W, Han F, Luo F. Trimethoxystilbene reduces nuclear factor kappa b, interleukin-6, and tumor necrosis factor-\u03b1 levels in rats with pulmonary artery hypertension. Biomed Res Int. 2019;2019:1219848.","DOI":"10.1155\/2019\/1219848"},{"key":"2023090109413389060_j_biol-2022-0650_ref_021","doi-asserted-by":"crossref","unstructured":"Zhu TT, Zhang WF, Yin YL, Liu YH, Song P, Xu J, et al. MicroRNA-140-5p targeting tumor necrosis factor-\u03b1 prevents pulmonary arterial hypertension. J Cell Physiol. 2019;234(6):9535\u201350.","DOI":"10.1002\/jcp.27642"},{"key":"2023090109413389060_j_biol-2022-0650_ref_022","unstructured":"Shen HP, Wu DW, Chen YF, Lian NF, Xu CS, Lian GL, et al. Role of TNF-\u03b1 in vascular remodeling in rats with chronic thromboembolic pulmonary hypertension. Zhonghua Jie He He Hu Xi Za Zhi. 2018;41(8):632\u20137."},{"key":"2023090109413389060_j_biol-2022-0650_ref_023","doi-asserted-by":"crossref","unstructured":"\u00c5berg M, Bj\u00f6rklund E, Wikstr\u00f6m G, Christersson C. Platelet-leukocyte aggregate formation and inflammation in patients with pulmonary arterial hypertension and CTEPH. Platelets. 2022;33(8):1199\u2013207.","DOI":"10.1080\/09537104.2022.2087867"},{"key":"2023090109413389060_j_biol-2022-0650_ref_024","unstructured":"Zhou MJ, Xing YJ, Yang J. NF-\u03baB inhibitor improves pulmonary vascular remodeling by reversing LPS-induced down-regulation of BMPRII. Sheng Li Xue Bao. 2020;72(5):541\u201350."},{"key":"2023090109413389060_j_biol-2022-0650_ref_025","doi-asserted-by":"crossref","unstructured":"Bao YR, Chen JW, Jiang Y, Wang LH, Xue R, Qian JX, et al. Sodium tanshinone II sulfonate a ameliorates hypoxia-induced pulmonary hypertension. Front Pharmacol. 2020;11:687.","DOI":"10.3389\/fphar.2020.00687"},{"key":"2023090109413389060_j_biol-2022-0650_ref_026","doi-asserted-by":"crossref","unstructured":"El Alam S, Pena E, Aguilera D, Siques P, Brito J. Inflammation in pulmonary hypertension and edema induced by hypobaric hypoxia exposure. Int J Mol Sci. 2022;23(20):12656.","DOI":"10.3390\/ijms232012656"}],"container-title":["Open Life Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/biol-2022-0650\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/biol-2022-0650\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T10:09:18Z","timestamp":1693562958000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/biol-2022-0650\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,1]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,6,14]]},"published-print":{"date-parts":[[2023,6,14]]}},"alternative-id":["10.1515\/biol-2022-0650"],"URL":"https:\/\/doi.org\/10.1515\/biol-2022-0650","relation":{},"ISSN":["2391-5412"],"issn-type":[{"value":"2391-5412","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,1]]},"article-number":"20220650"}}