PTP1B Implication in the Vascular Dysfunction Associated With Obstructive Sleep Apnea

University Hospital, Angers58 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Sleep Apnea Inflammation Atherosclerosis

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: baseline

Secondary Outcomes

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.

Time frame: 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.

Time frame: baseline

PTP1B Implication in the Vascular Dysfunction Associated With Obstructive Sleep Apnea

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes