{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T01:11:41Z","timestamp":1783473101081,"version":"3.55.0"},"reference-count":32,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T00:00:00Z","timestamp":1683849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pulmonary arterial hypertension (PAH) is a pathophysiological state of abnormally elevated pulmonary arterial pressure caused by drugs, inflammation, toxins, viruses, hypoxia, and other risk factors. We studied the therapeutic effect and target of tetramethylpyrazine (tetramethylpyrazine [TMP]; ligustrazine) in the treatment of PAH and we speculated that dramatic changes in myocardin levels can significantly affect the progression of PAH. In vivo, the results showed that administration of TMP significantly prolonged the survival of PAH rats by reducing the proliferative lesions, right ventricular systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), and the Fulton index in the heart and lung of PAH rats. In vitro, TMP can regulate the levels of smooth muscle protein 22\u2010alpha (SM22\u2010\u03b1), and myocardin as well as intracellular cytokines such as NO, transforming growth factor beta (TGF\u2010\u03b2), and connective tissue growth factor (CTGF) in a dose\u2010dependent manner (25, 50, or 100\u2009\u03bcM). Transfection of myocardin small interfering RNA (siRNA) aggravated the proliferation of pulmonary artery smooth muscle cells (PSMCs), and the regulatory effect of TMP on \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA) and osteopontin (OPN) disappeared. The application of 10\u2009nM estrogen receptor alpha (ER\u03b1) inhibitor MPP promoted the proliferation of PSMCs, but it does not affect the inhibition of TMP on PSMCs proliferation. Finally, we found that TMP promoted the nucleation of myocardin\u2010related transcription factor\u2010A (MRTF\u2010A) and combined it with myocardin. In conclusion, TMP can inhibit the transformation of PSMCs from the contractile phenotype to the proliferative phenotype by promoting the formation of the nuclear (MRTF\u2010A\/myocardin) transcription complex to treat PAH.<\/jats:p>","DOI":"10.1111\/cts.13534","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T05:36:17Z","timestamp":1682487377000},"page":"1369-1380","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ligustrazine alleviates pulmonary arterial hypertension in rats by promoting the formation of myocardin transcription complex in the nucleus of pulmonary artery smooth muscle cells"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2694-1389","authenticated-orcid":false,"given":"Xichao","family":"Yu","sequence":"first","affiliation":[{"name":"School of Medicine &amp; Holistic Integrative Medicine Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjie","family":"Wu","sequence":"additional","affiliation":[{"name":"The Third Clinical Medical College Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinhai","family":"Meng","sequence":"additional","affiliation":[{"name":"School of Medicine &amp; Holistic Integrative Medicine Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijie","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Medicine &amp; Holistic Integrative Medicine Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine &amp; Holistic Integrative Medicine Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine &amp; Holistic Integrative Medicine Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuewen","family":"Qi","sequence":"additional","affiliation":[{"name":"Craig High School  Janesville Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqun","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine The First Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine The First Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingli","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine The First Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine &amp; 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