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Open AccessArticle

SMAD4 Overexpression in Patients with Sleep Apnoea May Be Associated with Cardiometabolic Comorbidities

1
Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), 28029 Madrid, Spain
2
Respiratory Diseases Group, Respiratory Diseases Department, La Paz University Hospital, IdiPAZ, 28046 Madrid, Spain
3
The Innate Immune Response Group, La Paz University Hospital, IdiPAZ, 28046 Madrid, Spain
4
Faculty of Medicine, Autonomous University of Madrid, 28029 Madrid, Spain
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2020, 9(8), 2378; https://doi.org/10.3390/jcm9082378
Received: 28 May 2020 / Revised: 20 July 2020 / Accepted: 23 July 2020 / Published: 25 July 2020
(This article belongs to the Special Issue Sleep-Disordered Breathing in Cardiovascular Disease)
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 (TGFβ), 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 TGFβ signalling pathways. In this study, we evaluate Smad4 protein and mRNA expression from 52 newly diagnosed OSA patients, with an apnoea–hypopnoea index (AHI) ≥30 and 26 healthy volunteers. These analyses reveal that OSA patients exhibit high levels of SMAD4 which correlates with variation in HIF1α, 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. View Full-Text
Keywords: OSA; TGFβ; SMAD4; HIF1α; intermittent hypoxia; circadian rhythm OSA; TGFβ; SMAD4; HIF1α; intermittent hypoxia; circadian rhythm
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Díaz-García, E.; Jaureguizar, A.; Casitas, R.; García-Tovar, S.; Sánchez-Sánchez, B.; Zamarrón, E.; López-Collazo, E.; García-Río, F.; Cubillos-Zapata, C. SMAD4 Overexpression in Patients with Sleep Apnoea May Be Associated with Cardiometabolic Comorbidities. J. Clin. Med. 2020, 9, 2378.

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