SMAD4 Expression in Monocytes as a Potential Biomarker for Atherosclerosis Risk in Patients with Obstructive Sleep Apnea.
HIF1α
NLRP3
OSA
SMAD4
TF
TGF-β
atherosclerosis
hypoxia
inflammation
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
26 Apr 2023
26 Apr 2023
Historique:
received:
13
03
2023
revised:
14
04
2023
accepted:
25
04
2023
medline:
15
5
2023
pubmed:
13
5
2023
entrez:
13
5
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37175608
pii: ijms24097900
doi: 10.3390/ijms24097900
pmc: PMC10178665
pii:
doi:
Substances chimiques
Biomarkers
0
SMAD4 protein, human
0
Smad4 Protein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Instituto de Salud Carlos III
ID : PI22/01262
Organisme : Instituto de Salud Carlos III
ID : CP18/00028
Organisme : Instituto de Salud Carlos III
ID : PI19/01363
Organisme : Instituto de Salud Carlos III
ID : PI22/01257
Organisme : Instituto de Salud Carlos III
ID : PI19/01612
Organisme : Instituto de Salud Carlos III
ID : CD22/00033
Organisme : Instituto de Salud Carlos III
ID : PI21/01954
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