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Although rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR), has been reported to be effective in preventing aortopathies in mouse models, its mode of action has yet to be clarified. A mouse AD model that was created by the simultaneous administration of \u03b2-aminopropionitrile (BAPN) and angiotensin II (AngII) for 14 days. Rapamycin treatment was started either at day 1 or at day 7 of BAPN+AngII challenge, and continued throughout the observational period. Rapamycin was effective both in preventing AD development and in suppressing AD progression. On the other hand, gefitinib, an inhibitor of growth factor signaling, did not show such a beneficial effect, even though both rapamycin and gefitinib suppressed cell cycle activation in AD. Rapamycin suppressed cell cycle-related genes and induced muscle development-related genes in an AD-related gene expression network without a major impact on inflammation-related genes. Rapamycin augmented the activation of Akt1, Akt2, and Stat3, and maintained the contractile phenotype of aortic smooth muscle cells. These findings indicate that rapamycin was effective both in preventing the development and in suppressing the progression of AD, indicating the importance of the mTOR pathway in AD pathogenesis.<\/jats:p>","DOI":"10.3390\/ijms21093341","type":"journal-article","created":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T11:26:00Z","timestamp":1588937160000},"page":"3341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Therapeutic Effect of Rapamycin on Aortic Dissection in Mice"],"prefix":"10.3390","volume":"21","author":[{"given":"Makiko","family":"Hayashi-Hori","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Aoki","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, Kurume University, Kurume, Fukuoka 830-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Matsukuma","sequence":"additional","affiliation":[{"name":"Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryohei","family":"Majima","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohei","family":"Ito","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saki","family":"Hirakata","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norifumi","family":"Nishida","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Furusho","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4180-2857","authenticated-orcid":false,"given":"Satoko","family":"Ohno-Urabe","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Fukumoto","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,8]]},"reference":[{"key":"ref_1","unstructured":"Cronenwett, J.L., and Johnston, K.W. 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