SMAD4 Expression in Monocytes as a Potential Biomarker for Atherosclerosis Risk in Patients with Obstructive Sleep...

Area of Science:

• Cardiovascular Research
• Sleep Medicine
• Molecular Biology

Background:

• Obstructive sleep apnea (OSA) increases atherosclerosis and cardiovascular disease risk.
• Transforming growth factor-beta (TGF-β) pathway is critical in atherosclerosis.
• SMAD4, a key regulator of TGF-β, is elevated in OSA, particularly with cardiometabolic diseases.

Purpose of the Study:

• To analyze soluble and intracellular SMAD4 levels in OSA patients with/without early subclinical atherosclerosis (eSA).
• To investigate mechanisms of SMAD4 upregulation and release in OSA using in vitro and ex vivo models.

Main Methods:

• Quantification of soluble and intracellular SMAD4 in plasma and monocytes from OSA and non-apneic subjects.
• In vitro and ex vivo experiments to explore SMAD4 regulation and release mechanisms.

Main Results:

• Elevated soluble SMAD4 (sSMAD4) levels confirmed in OSA patients.
• sSMAD4 levels were significantly higher in OSA patients with eSA.
• SMAD4 overexpression observed in OSA monocytes.
• Intermittent hypoxia promotes SMAD4 upregulation and release, mediated by NLRP3.

Conclusions:

• sSMAD4 shows potential as a biomarker for atherosclerosis risk in OSA patients.
• Identified NLRP3-mediated mechanism for SMAD4 upregulation and release in OSA.
• Provides novel insights into molecular pathways linking OSA, atherosclerosis, and SMAD4.