Increased matrix metalloproteinases-9 after sleep in plasma and in monocytes of obstructive sleep apnea patients

Abstract

Aims: Obstructive sleep apnea is known to be a risk factor of coronary artery disease. Matrix metalloproteinases (MMPs) contribute to the instability and rupture of atherosclerotic plaque and acute coronary syndrome. The present study aimed to determine the correlation of MMPs including MMP-1, -2, -3 and -9 with the severity of obstructive sleep apnea (OSA).

Main methods: Peripheral blood was sampled before and after overnight polysomnography study from OSA patients. Plasma was processed for ELISA and zymography. Monocytes were isolated from peripheral blood and RNA was prepared for RT/real-time PCR.

Key findings: The plasma level of MMP-9, but not MMP-1, -2, and -3 and TIMP-1 was remarkably increased in OSA patients. The plasma MMP-9 level was considerably higher after sleep and the net difference was most significant in patients with severe OSA. The plasma MMP-9 activity was also demonstrated to be significantly higher after sleep. The mRNA expression of MMP-9 in monocytes not only correlated well to the plasma MMP-9 level in the patients, but also was found to be significantly higher in patients with severe OSA.

Significance: This study for the first time proves that the increase of plasma MMP-9 level in OSA patients is likely due to the up-regulated MMP-9 mRNA expression of monocytes in the peripheral blood.

Keywords: MMP-9; Monocyte; Obstructive sleep apnea; Polysomnography.