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Published ahead of print on September 10, 2004, doi:10.1164/rccm.200402-193OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 12, December 2004, 1354-1359

A more recent version of this article appeared on December 15, 2004
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Submitted on February 16, 2004
Accepted on September 4, 2004

Increased Levels and Activity of Matrix Metalloproteinase-9 in Obstructive Sleep Apnea Syndrome

Toshiyuki Tazaki1, Kenji Minoguchi1*, Takuya Yokoe1, Karen TR Samson1, Hideko Minoguchi1, Akihiro Tanaka1, Yoshio Watanabe1, and Mitsuru Adachi1

1 First Department of Internal Medicine, Showa University, Tokyo, Japan

* To whom correspondence should be addressed. E-mail: minochan{at}fn.catv.ne.jp.

Matrix metalloproteinases (MMPs) are involved in the pathogenesis of cardiovascular diseases. We examined serum levels of MMP-9 and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), activity of MMP-9, and the effect of nasal continuous positive airway pressure (nCPAP) in patients with obstructive sleep apnea syndrome (OSAS). After polysomnography venous blood was collected at 5 a.m. from 44 patients with OSAS and 18 obese control subjects, and serum levels of MMP-9, TIMP-1, and enzymatic activity of MMP-9 were measured. In addition, the effects of 1 months[[rad]] treatment with nCPAP were studied in patients with moderate to severe OSAS. Although serum levels of MMP-9 (p < 0.05) and MMP-9 activity (p < 0.01) were higher in patients with OSAS than in obese control subjects, TIMP-1 levels did not differ significantly. In patients with OSAS the severity of OSAS was the primary factor influencing levels (p < 0.01) and activity (p < 0.01) of MMP-9. nCPAP significantly decreased serum levels (p < 0.01) and activity (p < 0.001) of MMP-9 but not affect TIMP-1 levels. Therefore, OSAS may increase risks of cardiovascular morbidity, and nCPAP might be useful for decreasing these risks.
Key words: Sleep apnea, cardiovascular disease, metalloproteinase, atherosclerosis, cytokine




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