Neopterin is associated with plaque inflammation and destabilization in human coronary atherosclerotic lesions

Taichi Adachi ¹, Takahiko Naruko ^1*, Akira Itoh ¹, Ryushi Komatsu ¹, Yukio Abe ¹, Nobuyuki Shirai ², Hajime Yamashita ², Shoichi Ehara ², Masashi Nakagawa ², Chizuko Kitabayashi ², Yoshihiro Ikura ², Masahiko Ohsawa ², Minoru Yoshiyama ², Kazuo Haze ¹ and Makiko Ueda ²

¹ Osaka City General Hospital, Japan
² Osaka City University Graduate School of Medicine, Japan

^* To whom correspondence should be addressed. E-mail: tmnaruko{at}msic.med.osaka-cu.ac.jp.

Accepted 6 March 2007

Abstract

Objective Previous studies have shown that recent activation of the imflammatory response in coronary atherosclerotic lesions contributes to rapid progressive plaque destabilization. Neopterin, a by-product of the guanosine triphosphate pathway, is produced by activated macrophages and serves as an activation marker for monocytes/macrophages. To elucidate the role of neopterin in coronary plaque destabilization, we immunohistochemically studied the presence of neopterin in coronary atherectomy specimens obtained from patients with stable angina pectoris (SAP) and unstable angina pectoris (UAP).

Design and patients All patients underwent atherectomy of the primary atherosclerotic lesions responsible for SAP (n=25) and UAP (n=25). Frozen samples were studied with antibodies against smooth muscle cells, macrophages, T cells, neutrophils, and neopterin.

Results In 22 of the 25 patients with UAP, abundant neopterin-positive macrophages were found at the sites of coronary culprit lesions. However, in 25 lesions from SAP patients, only 11 lesions showed neopterin positivity. Quantitatively, the neopterin-positive macrophage score was significantly higher (P<0.0001) in patients with UAP than in patients with SAP. Moreover, the neopterin-positive macrophage score showed a significant positive correlation with the number of neutrophils or T cells, respectively (neutrophils, r = 0.55, P<0.0001; T cells, r = 0.70, P<0.0001).

Conclusions Neopterin can be considered as one of the significant factors in the process of plaque inflammation and destabilization in human coronary atherosclerotic lesions. However, itfs exact role in the process needs to be further investigated.

Keywords: angina, atherosclerosis, inflammation, neopterin

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