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European Heart Journal 2003 24(24):2180-2185; doi:10.1016/j.ehj.2003.09.022
Copyright © 2003 by the European Society of Cardiology.
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Clinical research

Correlation of oxidative stress with activity of matrix metalloproteinase in patients with coronary artery disease

Possible role for left ventricular remodelling

Kunihiko Kamedaa, Toshiro Matsunagaa, Naoki Abea, Hiroyuki Hanadaa, Hiroshi Ishizakaa, Hirotsugu Onoa, Masayuki Saitoha, Kozo Fukuib, Ikuo Fukudab, Tomohiro Osanaia and Ken Okumuraa,*

a The Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan
b First Department of Surgery, Hirosaki University School of Medicine, Hirosaki, Japan

* Correspondence to: Ken Okumura, MD, Second Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifu, Hirosaki 036-8562, Japan. Tel: +81-172-39-5057; Fax: +81-172-35-9190
E-mail address: okumura{at}cc.hirosaki-u.ac.jp

Received 23 January 2003; revised 13 September 2003; accepted 19 September 2003

Abstract

Aim Oxidative stress is implicated in the progression of heart failure, and matrix metalloproteinase (MMP) activity is increased in patients with congestive heart failure. We examined the role of oxidative stress on MMP activity in humans.

Methods and results We measured the MMP activity and the level of 8-iso-prostagandin F2{alpha} (8-iso-PGF2{alpha}), a specific and quantitative maker of oxidant stress, in the pericardial fluid (PF) in 47 consecutive patients with coronary artery disease who underwent coronary artery bypass surgery. Zymography of PF showed bands at 92–85kDa (MMP-9) and 72–65kDa (MMP-2). The MMP activity was expressed as the ratio to MMP-2 standard. MMP-2, MMP-9 and total gelatinolysis activities were positively correlated with left ventricular end-diastolic volume index (LVEDVI), and MMP-2 and total gelatinolysis activities were also positively correlated with LV end-systolic volume index. Moreover, MMP-2, MMP-9 and total gelatinolysis activities were all positively correlated with pericardial level of 8-iso-PGF2{alpha}. Also, LVDEVI was positively correlated with pericardial level of 8-iso-PGF2{alpha}.

Conclusion Oxidative stress may play an important role in the regulation of MMP activity. Augmented MMP activity may be involved in the development of ventricular remodelling in patients with coronary artery disease.

Key Words: Matrix metalloproteinase • Oxidative stress • Ventricular remodelling


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