SMAD4 expression in monocytes as a potential biomarker for atherosclerosis risk in patients with obstructive sleep apnea

Díaz-García, Elena ; García-Sánchez, Aldara ; Sánz-Rubio, David ; Alfaro, Enrique ; López-Fernández, Cristina ; Casitas, Raquel ; Mañas Baena, Eva ; Cano-Pumarega, Irene ; Cubero, Pablo ; Marin-Oto, Marta (Universidad de Zaragoza) ; López-Collazo, Eduardo ; Marin, José María (Universidad de Zaragoza) ; García-Río, Francisco ; Cubillos-Zapata, Carolina

Resumen: Obstructive sleep apnea (OSA) patients are at special risk of suffering atherosclerosis, leading to major cardiovascular diseases. Notably, the transforming growth factor (TGF-β) plays a crucial role in the development and progression of atherosclerosis. In this context, the central regulator of TGF-β pathway, SMAD4 (small mother against decapentaplegic homolog 4), has been previously reported to be augmented in OSA patients, which levels were even higher in patients with concomitant cardiometabolic diseases. Here, we analyzed soluble and intracellular SMAD4 levels in plasma and monocytes from OSA patients and non-apneic subjects, with or without early subclinical atherosclerosis (eSA). In addition, we used in vitro and ex vivo models to explore the mechanisms underlying SMAD4 upregulation and release. Our study confirmed elevated sSMAD4 levels in OSA patients and identified that its levels were even higher in those OSA patients with eSA. Moreover, we demonstrated that SMAD4 is overexpressed in OSA monocytes and that intermittent hypoxia contributes to SMAD4 upregulation and release in a process mediated by NLRP3. In conclusion, this study highlights the potential role of sSMAD4 as a biomarker for atherosclerosis risk in OSA patients and provides new insights into the mechanisms underlying its upregulation and release to the extracellular space.

Idioma: Inglés

DOI: 10.3390/ijms24097900

Año: 2023

Publicado en: International Journal of Molecular Sciences 24, 9 (2023), 7900 [15 pp.]
ISSN: 1661-6596

Factor impacto JCR: 4.9 (2023)

Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 66 / 313 = 0.211 (2023) - Q1 - T1
Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 68 / 231 = 0.294 (2023) - Q2 - T1

Factor impacto CITESCORE: 8.1 - Spectroscopy (Q1) - Computer Science Applications (Q1) - Physical and Theoretical Chemistry (Q1) - Inorganic Chemistry (Q1) - Organic Chemistry (Q1) - Molecular Biology (Q2) - Catalysis (Q2)

Factor impacto SCIMAGO: 1.179 - Medicine (miscellaneous) (Q1) - Physical and Theoretical Chemistry (Q1) - Computer Science Applications (Q1) - Inorganic Chemistry (Q1) - Spectroscopy (Q1) - Organic Chemistry (Q1) - Molecular Biology (Q2) - Catalysis (Q2)

Financiación: info:eu-repo/grantAgreement/ES/ISCIII-FEDER-FIS/PI18-01524
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI21-01954

Tipo y forma: Article (Published version)

Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)