{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T03:54:42Z","timestamp":1774151682214,"version":"3.50.1"},"reference-count":53,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T00:00:00Z","timestamp":1734998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine","award":["ZYYCXTD-D-202207"],"award-info":[{"award-number":["ZYYCXTD-D-202207"]}]},{"name":"Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine","award":["82274198"],"award-info":[{"award-number":["82274198"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["ZYYCXTD-D-202207"],"award-info":[{"award-number":["ZYYCXTD-D-202207"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82274198"],"award-info":[{"award-number":["82274198"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic exposure to high altitudes causes pathophysiological cardiac changes that are characterized by cardiac dysfunction, cardiac hypertrophy, and decreased energy reserves. However, finding specific pharmacological interventions for these pathophysiological changes is challenging. In this study, we identified tetramethylpyrazine (TMP) as a promising drug candidate for cardiac dysfunction caused by simulated high-altitude exposure. By utilizing hypobaric chambers to simulate high-altitude environments, we found that TMP improved cardiac function, alleviated cardiac hypertrophy, and reduced myocardial injury in hypobaric hypoxic mice. RNA sequencing showed that TMP also upregulated heart-contraction-related genes that were suppressed by hypobaric hypoxia exposure. Mechanistically, TMP inhibited hypobaric hypoxia-induced cardiac Ca2+\/calmodulin-dependent kinase II (CaMKII) activation and exerted cardioprotective effects by inhibiting CaMKII. Our data suggest that TMP application may be a promising approach for treating high-altitude-induced cardiac dysfunction, and they highlight the crucial role of CaMKII in hypobaric hypoxia-induced cardiac pathophysiology.<\/jats:p>","DOI":"10.3390\/ijms26010054","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T10:58:32Z","timestamp":1735037912000},"page":"54","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Tetramethylpyrazine Protects Against Chronic Hypobaric Hypoxia-Induced Cardiac Dysfunction by Inhibiting CaMKII Activation in a Mouse Model Study"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3306-4484","authenticated-orcid":false,"given":"Pengfei","family":"Zhang","sequence":"first","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0643-1974","authenticated-orcid":false,"given":"Huifang","family":"Deng","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiong","family":"Lan","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pan","family":"Shen","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijie","family":"Bai","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaoji","family":"Huangfu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ningning","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengrong","family":"Xiao","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0138-8938","authenticated-orcid":false,"given":"Yehui","family":"Gao","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Sun","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiamiao","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Guo","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0435-7261","authenticated-orcid":false,"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Gao","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"},{"name":"State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing 100853, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1136\/hrt.69.1.3","article-title":"Hypoxia and the heart","volume":"69","author":"Davies","year":"1993","journal-title":"Br. 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