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

Obstructive sleep apnoea (OSA) is associated with several diseases related to metabolic andcardiovascular risk. Although the mechanisms involved in the development of these disorders mayvary, OSA patients frequently present an increase in transforming growth factor beta (TGF?), theactivity 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 ofsignal transducers and acts as a central mediator of TGF? signalling pathways. In this study, weevaluate Smad4 protein and mRNA expression from 52 newly diagnosed OSA patients, with anapnoea–hypopnoea index (AHI) ?30 and 26 healthy volunteers. These analyses reveal that OSApatients exhibit high levels of SMAD4 which correlates with variation in HIF1?, mTOR and circadiangenes. Moreover, we associated high concentrations of Smad4 plasma protein with the presence ofdiabetes, dyslipidaemia and hypertension in these patients. Results suggest that increased levels ofSMAD4, mediated by intermittent hypoxaemia and circadian rhythm deregulation, may be associatedwith cardiometabolic comorbidities in patients with sleep apnoea.