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Leukotriene B₄: early mediator of atherosclerosis in obstructive sleep apnoea?

¹ INSERM, ERI7, ² Grenoble University 1, Faculté de Médecine, IFR1, ³ BP217, Pharmacology Laboratory, ⁴ BP217, EFCR Laboratory, and ⁵ BP217, Cardiology Unit, A. Michallon Hospital, Centre Hospitalier Universitaire, and ⁶ INSERM 8777, Grenoble, France.

CORRESPONDENCE: F. Stanke-Labesque, Laboratoire de Pharmacologie, Centre Hospitalier Universitaire, Hôpital A. Michallon, BP 217, 38043 Grenoble Cedex 9, France. Fax: 33 476768938. E-mail: FStanke{at}chu-grenoble.fr

Keywords: Atherosclerosis, leukotriene B₄, polymorphonuclear cells, sleep apnoea

Received: October 17, 2007
Accepted February 11, 2008

Severity of oxygen desaturation is predictive of early atherosclerosis in obstructive sleep apnoea (OSA). Leukotriene (LT)B₄ is a lipid mediator involved in atherogenesis.

In 40 non-obese OSA patients, free of a cardiovascular history, and 20 healthy volunteers, the following were evaluated: 1) LTB₄ production by polymorphonuclear leukocytes (PMNs) stimulated with A23187 [GenBank] ; and 2) the relationships between LTB₄ production and both OSA severity and infraclinical atherosclerosis markers. The effect of continuous positive airway pressure (CPAP) on LTB₄ production was also studied. An overnight sleep study was followed by first-morning blood sampling. Isolated PMNs were stimulated with A23187 [GenBank] in order to induce LTB₄ production, which was measured by liquid chromatography–tandem mass spectrometry. Carotid intima-media thickness (IMT) and luminal diameter were measured in subset groups of 28 OSA patients and 11 controls.

LTB₄ production was increased in OSA patients compared with controls. LTB₄ levels correlated with the mean and minimal arterial oxygen saturation (S_a,O2). LTB₄ production correlated with luminal diameter data in patients with a mean S_a,O2 of 94% but not with IMT. Lastly, CPAP significantly reduced LTB₄ production by 50%.

Leukotriene B₄ production is increased in obstructive sleep apnoea in relation to oxygen desaturation. Leukotriene B₄ could promote early vascular remodelling in moderate-to-severe hypoxic obstructive sleep apnoea patients.