{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T06:03:38Z","timestamp":1770703418507,"version":"3.49.0"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T00:00:00Z","timestamp":1549497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education","award":["NRF-2015R1D1A1A01056798"],"award-info":[{"award-number":["NRF-2015R1D1A1A01056798"]}]},{"name":"Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education","award":["NRF-2018R1D1A1B07047213"],"award-info":[{"award-number":["NRF-2018R1D1A1B07047213"]}]},{"name":"Korea Healthcare Technology R&D Project, Ministry of Health & Welfare","award":["HI13C1527"],"award-info":[{"award-number":["HI13C1527"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Here, we report that LMK235, a class I and histone deacetylase (HDAC6)\u2010preferential HDAC inhibitor, reduces hypertension via inhibition of vascular contraction and vessel hypertrophy. Angiotensin II\u2010infusion mice and spontaneously hypertensive rats (SHRs) were used to test the anti\u2010hypertensive effect of LMK235. Daily injection of LMK235 lowered angiotensin II\u2010induced systolic blood pressure (BP). A reduction in systolic BP in SHRs was observed on the second day when SHRs were treated with 3\u00a0mg\/kg LMK235 every 3\u00a0days. However, LMK235 treatment did not affect angiotensin\u2010converting enzyme 1 and angiotensin II receptor mRNA expression in either hypertensive model. LMK235, acting via the nitric oxide pathway, facilitated the relaxing of vascular contractions induced by a thromboxane A2 agonist in the rat aortic and mesenteric artery ring test. In addition, LMK235 increased nitric oxide production in HUVECs and inhibited the increasing of aortic wall thickness in both animal hypertensive models. LMK235 decreased the enhanced cell cycle\u2010related genes cyclin D1 and E2F3 in angiotensin II\u2010infusion mice and restored the decreased p21 expression. In addition, LMK235 suppressed calcium calmodulin\u2010dependent protein kinase II (CaMKII) \u03b1, which is related to vascular smooth muscle cell proliferation. Inhibition or knockdown of HDAC5 blocked the CaMKII\u03b1\u2010induced cell cycle gene expression. Immunoprecipitation demonstrated that class I HDACs were involved in the inhibition of CaMKII \u03b1\u2010induced HDAC4\/5 by LMK235. We suggest that LMK235 should be further investigated for its use in the development of new therapeutic options to treat hypertension via reducing vascular hyperplasia or vasoconstriction.<\/jats:p>","DOI":"10.1111\/jcmm.14188","type":"journal-article","created":{"date-parts":[[2019,2,8]],"date-time":"2019-02-08T04:16:54Z","timestamp":1549599414000},"page":"2801-2812","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Histone deacetylase inhibitor LMK235 attenuates vascular constriction and aortic remodelling in hypertension"],"prefix":"10.1111","volume":"23","author":[{"given":"Sin Young","family":"Choi","sequence":"first","affiliation":[{"name":"Heart Research Center of Chonnam National University Hospital Gwangju Republic of Korea"},{"name":"Hypertension Heart Failure Research Center Chonnam National University Hospital Gwangju Republic of Korea"},{"name":"Molecular Medicine, Brain Korea 21 PLUS Chonnam National University Graduate School  Gwangju Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9774-4828","authenticated-orcid":false,"given":"Hae Jin","family":"Kee","sequence":"additional","affiliation":[{"name":"Heart Research Center of Chonnam National University Hospital Gwangju Republic of Korea"},{"name":"Hypertension Heart Failure Research Center Chonnam National University Hospital Gwangju Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simei","family":"Sun","sequence":"additional","affiliation":[{"name":"Heart Research Center of Chonnam National University Hospital Gwangju Republic of Korea"},{"name":"Hypertension Heart Failure Research Center Chonnam National University Hospital Gwangju Republic of Korea"},{"name":"Molecular Medicine, Brain Korea 21 PLUS Chonnam National University Graduate School  Gwangju Republic of Korea"},{"name":"Zhoushan Hospital, Zhejiang University School of Medicine Zhoushan Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Mi","family":"Seok","sequence":"additional","affiliation":[{"name":"National Development Institute of Korean Medicine Gyeongsan\u2010si Gyeongsangbuk\u2010do Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhee","family":"Ryu","sequence":"additional","affiliation":[{"name":"Heart Research Center of Chonnam National University Hospital Gwangju Republic of Korea"},{"name":"Hypertension Heart Failure Research Center Chonnam National University Hospital Gwangju Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gwi Ran","family":"Kim","sequence":"additional","affiliation":[{"name":"Heart Research Center of Chonnam National University Hospital Gwangju Republic of Korea"},{"name":"Hypertension Heart Failure Research Center Chonnam National University Hospital Gwangju Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung\u2010Jung","family":"Kee","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Chonnam National University, Medical School and Hospital Gwangju Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Pflieger","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical and Medicinal Chemistry Heinrich Heine University D\u00fcsseldorf D\u00fcsseldorf Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Kurz","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical and Medicinal Chemistry Heinrich Heine University D\u00fcsseldorf D\u00fcsseldorf Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias U.","family":"Kassack","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical and Medicinal Chemistry Heinrich Heine 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