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European Heart Journal Advance Access published online on June 25, 2009
European Heart Journal, doi:10.1093/eurheartj/ehp257
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org

Enhanced expression of haemoglobin scavenger receptor in accumulated macrophages of culprit lesions in acute coronary syndromes

Kei Yunoki1, Takahiko Naruko1, Ryushi Komatsu1, Shoichi Ehara2, Nobuyuki Shirai2, Kenichi Sugioka2, Masashi Nakagawa3, Chizuko Kitabayashi3, Yoshihiro Ikura3, Akira Itoh1, Kengo Kusano4, Tohru Ohe4, Kazuo Haze1, Anton E. Becker5 and Makiko Ueda3,*

1 Department of Cardiology, Osaka City General Hospital, Osaka, Japan
2 Department of Cardiology and Internal Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan
3 Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan
4 Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Okayama, Japan
5 Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Received 29 November 2008; revised 19 March 2009; accepted 29 April 2009 * Corresponding author. Tel: +81 6 6645 3740, Fax: +81 6 6645 3742, Email: maki{at}med.osaka-cu.ac.jp

Aims: Effective clearance of extracellular haemoglobin (Hb) is thought to limit systemic oxidative heme toxicity, which is presumed to contribute to the pathogenesis of plaque instability. We immunohistochemically examined the relationship between intraplaque haemorrhage, 4-HNE (4-hydroxy-2-nonenal), an index of lipid peroxidation, and the Hb scavenger receptor (CD163), using coronary atherectomy specimens from 74 patients with stable angina pectoris (SAP, n = 39) or unstable angina pectoris (UAP, n = 35).

Methods and results: Atherectomy samples were stained with antibodies against glycophorin A (a protein specific to erythrocyte membranes), CD31, 4-HNE, and CD163. Quantitative analysis demonstrated that glycophorin A-positive areas, 4-HNE-positive macrophage score, and CD163-positive macrophage score in UAP patients were significantly higher (glycophorin A, P < 0.0001; 4-HNE-positive macrophage score, P < 0.0001; CD163-positive macrophage score, P < 0.0005) than in SAP patients. The percentage of the glycophorin A-positive area showed a significant positive correlation with the number of CD31-positive microvessels and the 4-HNE-positive macrophage score (microvessels, R = 0.59, P < 0.0001; 4-HNE, R = 0.59, P < 0.0001). Moreover, the CD163-positive macrophage score was positively correlated with glycophorin A-positive area and the 4-HNE-positive macrophage score (glycophorin A, R = 0.58, P < 0.0001; 4-HNE, R = 0.53, P < 0.0001).

Conclusion: These findings suggest a positive association among intraplaque haemorrhage, enhanced expression of Hb scavenger receptor, and lipid peroxidation in human unstable plaques.

Key Words: Atherosclerosis • Coronary disease • Angina • Lipoproteins


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