078 - Circulating microparticles and endothelial dysfunction in obstructive sleep apnea syndrome - 05/12/08

Introduction: Endothelial dysfunction plays a role in the increased cardiovascular morbidity associated with obstructive sleep apnea syndrome (OSAS). Microparticles (MPs) are membrane vesicles released during cell activation and apoptosis. Elevated levels of circulating MPs have been detected in pathological states associated with vascular alteration including endothelial dysfunction. We investigated the role of MPs on endothelial function in OSAS. Of particular interest is to test their effects on nitric oxide (NO) and reactive oxygen species (ROS) production in endothelial cells.

Methods: Blood sample were obtained and endothelial function was assessed using iontophoresis laser doppler from 19 OSAS patients without any other cardiovascular comorbidities and 13 healthy subjects. MPs concentration and origin were assessed using flow cytometer and investigating the expression of membrane-specific antigens. MPs from patients and control subjects were used to treat human endothelial cell line Eahy 926 for 24h. Then, NO production was evaluated by electron paramagnetic resonance.

Results: Endothelial function was impaired in OSAS subjects compared with matched controls and correlated negatively with the number of nocturnal 3% oxygen desaturations (n=24, p=0.03). Patients with OSAS displayed increased circulating levels of MPs from granulocytes (CD66b+) and MPs harbouring L-sélectine (CD62L+) compared to controls (p=0.014; p=0.015 respectively). In vitro treatment of endothelial cells with MPs from OSAS patients reduced NO production when compared either to untreated endothelial cells or those incubated with MPs from control patients (n=8, p=0.03) with no effect on ROS production. Furthermore, MPs from granulocytes levels correlated positively with nocturnes desaturations (r=0.39; p=0.045) and negatively with NO in vitro production (r=-0.5; p=0.041).

Conclusion: Our preliminary results provide evidence for a dose effect of nocturnal desaturation on endothelial dysfunction in OSAS. The capacity of MPs from OSAS patients to reduce endothelial NO production accounts for this endothelial dysfunction, and may be mediated by MPs from granulocytes.