{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T08:55:49Z","timestamp":1790153749852,"version":"4.0.1"},"reference-count":62,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,25]],"date-time":"2020-07-25T00:00:00Z","timestamp":1595635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondo de Investigaci\u00f3n Sanitaria (FIS) and Fondos FEDER","award":["PI13\/01512"],"award-info":[{"award-number":["PI13\/01512"]}]},{"name":"Fondo de Investigaci\u00f3n Sanitaria (FIS) and Fondos FEDER","award":["PI16\/00201"],"award-info":[{"award-number":["PI16\/00201"]}]},{"name":"Fondo de Investigaci\u00f3n Sanitaria (FIS) and Fondos FEDER","award":["PI19\/01363"],"award-info":[{"award-number":["PI19\/01363"]}]},{"name":"Miguel Servet, Instituto de Salud Carlos III","award":["CP18\/00028"],"award-info":[{"award-number":["CP18\/00028"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Obstructive sleep apnoea (OSA) is associated with several diseases related to metabolic and cardiovascular risk. Although the mechanisms involved in the development of these disorders may vary, OSA patients frequently present an increase in transforming growth factor beta (TGF\u03b2), the activity of which is higher still in patients with hypertension, diabetes or cardiovascular morbidity. Smad4 is a member of the small mother against decapentaplegic homologue (Smad) family of signal transducers and acts as a central mediator of TGF\u03b2 signalling pathways. In this study, we evaluate Smad4 protein and mRNA expression from 52 newly diagnosed OSA patients, with an apnoea\u2013hypopnoea index (AHI) \u226530 and 26 healthy volunteers. These analyses reveal that OSA patients exhibit high levels of SMAD4 which correlates with variation in HIF1\u03b1, mTOR and circadian genes. Moreover, we associated high concentrations of Smad4 plasma protein with the presence of diabetes, dyslipidaemia and hypertension in these patients. Results suggest that increased levels of SMAD4, mediated by intermittent hypoxaemia and circadian rhythm deregulation, may be associated with cardiometabolic comorbidities in patients with sleep apnoea.<\/jats:p>","DOI":"10.3390\/jcm9082378","type":"journal-article","created":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T04:39:50Z","timestamp":1595824790000},"page":"2378","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["SMAD4 Overexpression in Patients with Sleep Apnoea May Be Associated with Cardiometabolic Comorbidities"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4549-0678","authenticated-orcid":false,"given":"Elena","family":"D\u00edaz-Garc\u00eda","sequence":"first","affiliation":[{"name":"Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), 28029 Madrid, Spain"},{"name":"Respiratory Diseases Group, Respiratory Diseases Department, La Paz University Hospital, IdiPAZ, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5467-1203","authenticated-orcid":false,"given":"Ana","family":"Jaureguizar","sequence":"additional","affiliation":[{"name":"Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), 28029 Madrid, Spain"},{"name":"Respiratory Diseases Group, Respiratory Diseases Department, La Paz University Hospital, IdiPAZ, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Casitas","sequence":"additional","affiliation":[{"name":"Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), 28029 Madrid, Spain"},{"name":"Respiratory Diseases Group, Respiratory Diseases Department, La Paz University Hospital, IdiPAZ, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Garc\u00eda-Tovar","sequence":"additional","affiliation":[{"name":"Respiratory Diseases Group, Respiratory Diseases Department, La Paz University Hospital, IdiPAZ, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bego\u00f1a","family":"S\u00e1nchez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), 28029 Madrid, Spain"},{"name":"Respiratory Diseases Group, Respiratory Diseases Department, La Paz University Hospital, IdiPAZ, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"Zamarr\u00f3n","sequence":"additional","affiliation":[{"name":"Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), 28029 Madrid, Spain"},{"name":"Respiratory Diseases Group, Respiratory Diseases Department, La Paz University Hospital, IdiPAZ, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"L\u00f3pez-Collazo","sequence":"additional","affiliation":[{"name":"Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), 28029 Madrid, Spain"},{"name":"The Innate Immune Response Group, La Paz University Hospital, IdiPAZ, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7227-2238","authenticated-orcid":false,"given":"Francisco","family":"Garc\u00eda-R\u00edo","sequence":"additional","affiliation":[{"name":"Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), 28029 Madrid, Spain"},{"name":"Respiratory Diseases Group, Respiratory Diseases Department, La Paz University Hospital, IdiPAZ, 28046 Madrid, Spain"},{"name":"Faculty of Medicine, Autonomous University of Madrid, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1948-4514","authenticated-orcid":false,"given":"Carolina","family":"Cubillos-Zapata","sequence":"additional","affiliation":[{"name":"Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), 28029 Madrid, Spain"},{"name":"Respiratory Diseases Group, Respiratory Diseases Department, La Paz University Hospital, IdiPAZ, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S2213-2600(19)30198-5","article-title":"Estimation of the global prevalence and burden of obstructive sleep apnoea: A literature-based analysis","volume":"7","author":"Benjafield","year":"2019","journal-title":"Lancet Respir. 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