PTP1B Implication in the Vascular Dysfunction Associated With Obstructive Sleep Apnea

Study Overview
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Brief Summary
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Obstructive sleep apnea (OSA) syndrome is associated with increased vascular dysfunction and atherosclerosis. Especially, it has been shown that OSA associated intermittent hypoxia represents a pro inflammatory stimulus resulting in macrophage polarization. Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin signaling pathways involved in atherosclerosis. It has been shown that myeloid PTP1B deficiency protects against atherosclerosis. As hypoxia has also been shown to increase PTP1B expression and activity, this study will evaluate the myeloid PTP1B expression and activity in patients with OSA as compared to controls and will investigate myeloid PTP1B involvement in the vascular pro inflammatory precess described in OSA.

Official Title
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PTP1B Implication in the Vascular Dysfunction Associated With Obstructive Sleep Apnea

Conditions
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Sleep Apnea, Inflammation, Atherosclerosis

Intervention / Treatment
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* Other: myeloid PTP1B expression analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Overnight polysomnographic recording for suspected OSA Apnea hypopnea index ≥ 15 per hour for OSA patients Apnea hypopnea index < 15 per hour for non OSA patients Exclusion Criteria: past history of cardiovascular diseases diabetes dyslipidemia hypertension obesity (body mass index > 35 kg/m2 past history or ongoing inflammatory diseases cognition impairment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: patients with OSA 'apnea hypopnea index ≥ 15 per hour) as compared to controls (an apnea hypopnea index < 15 per hour)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: OSA patients<br>30 patients investigated for suspected OSA with an apnea hypopnea index ≥ 15 per hour | Other: myeloid PTP1B expression analysis<br>* peripheral blood macrophage PTP1B expression<br>|
| Other: non OSA patients<br>30 patients investigated for suspected OSA with an apnea hypopnea index < 15 per hour | Other: myeloid PTP1B expression analysis<br>* peripheral blood macrophage PTP1B expression<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| myeloid PTP1B expression | Peripheral blood will be collected from OSA and non OSA patients. Macrophage will be isolated by specific centrifugation. PTP1B expression will be assessed by Western Blot. | baseline | 
| myeloid PTP1B activity | Peripheral blood will be collected from OSA and non OSA patients. Macrophage will be isolated by specific centrifugation. PTP1B activity will be assessed by specific colorimetric assay. | baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PTP1B exosomal expression. | Peripheral blood will be collected from OSA and non OSA patients. Exosomes will be isolated by consecutive centrifugations. PTP1B expression will be assessed by Western Blot. | baseline | 
| in vitro PTP1B implication on macrophage inflammatory response | Macrophage isolated from patients will be stimulated by pro inflammatory agents (IL6, TNF alpha) in the presence and absence of PTP1B inhibitor (MSI-1436). The inflammatory response will be assessed by measuring inflammatory cytokines in the supernatant by ELISA. | baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PTP1B, macrophage