{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:22:16Z","timestamp":1789996936657,"version":"4.0.1"},"reference-count":106,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T00:00:00Z","timestamp":1559347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia (IH) and is a risk factor for cardiovascular diseases (e.g., atherosclerosis) and chronic inflammatory diseases (CID). The excessive proliferation of vascular smooth muscle cells (VSMCs) plays a pivotal role in the progression of atherosclerosis. Hypoxia-inducible factor-1 and nuclear factor-\u03baB are thought to be the main factors involved in responses to IH and in regulating adaptations or inflammation pathways, however, further evidence is needed to demonstrate the underlying mechanisms of this process in VSMCs. Furthermore, few studies of IH have examined smooth muscle cell responses. Our previous studies demonstrated that increased interleukin (IL)-6, epidermal growth factor family ligands, and erbB2 receptor, some of which amplify inflammation and, consequently, induce CID, were induced by IH and were involved in the proliferation of VSMCs. Since IH increased IL-6 and epiregulin expression in VSMCs, the same phenomenon may also occur in other smooth muscle cells, and, consequently, may be related to the incidence or progression of several diseases. In the present review, we describe how IH can induce the excessive proliferation of VSMCs and we develop the suggestion that other CID may be related to the effects of IH on other smooth muscle cells.<\/jats:p>","DOI":"10.3390\/ijms20112706","type":"journal-article","created":{"date-parts":[[2019,6,3]],"date-time":"2019-06-03T02:08:40Z","timestamp":1559527720000},"page":"2706","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Proliferative Pathways of Vascular Smooth Muscle Cells in Response to Intermittent Hypoxia"],"prefix":"10.3390","volume":"20","author":[{"given":"Yoji","family":"Kyotani","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4066-0199","authenticated-orcid":false,"given":"Shin","family":"Takasawa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Yoshizumi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"479","DOI":"10.5664\/jcsm.6506","article-title":"Clinical Practice Guideline for Diagnostic Testing for Adult Obstructive Sleep Apnea: An American Academy of Sleep Medicine Clinical Practice Guideline","volume":"13","author":"Kapur","year":"2017","journal-title":"J. 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