Adachi T, Naruko T, Itoh A, Komatsu R, Abe Y, Shirai N, Yamashita H, Ehara S, Nakagawa M, Kitabayashi C, Ikura Y, Ohsawa M, Yoshiyama M, Haze K, Ueda M
Department of Cardiology, Osaka City General Hospital, 2-13-22, Miyakojima-hondori, Miyakojima-ku, Osaka 534-0021, Japan.
Heart. 2007 Dec;93(12):1537-41. doi: 10.1136/hrt.2006.109736. Epub 2007 Jun 17.
Previous studies have shown that recent activation of the inflammatory response in coronary atherosclerotic lesions contributes to rapid progressive plaque destabilisation. 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 destabilisation by immunohistochemical study of the presence of neopterin in coronary atherectomy specimens obtained from patients with stable angina pectoris (SAP) and unstable angina pectoris (UAP).
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.
In 22/25 patients with UAP, abundant neopterin-positive macrophages were found at the sites of coronary culprit lesions. However, in 25 lesions from patients with SAP, only 11 lesions showed neopterin positivity. Quantitatively, the neopterin-positive macrophage score was significantly higher (p<0.001) 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<0.001; T cells, r = 0.70, p<0.001).
Neopterin can be considered as one of the significant factors in the process of plaque inflammation and destabilisation in human coronary atherosclerotic lesions. Its exact role in the process needs to be investigated further.
先前的研究表明,冠状动脉粥样硬化病变中炎症反应的近期激活会导致斑块快速进展性不稳定。新蝶呤是三磷酸鸟苷途径的副产物,由活化的巨噬细胞产生,可作为单核细胞/巨噬细胞的活化标志物。
通过免疫组织化学研究稳定型心绞痛(SAP)和不稳定型心绞痛(UAP)患者冠状动脉旋切标本中是否存在新蝶呤,以阐明新蝶呤在冠状动脉斑块不稳定中的作用。
所有患者均接受了对导致SAP(n = 25)和UAP(n = 25)的原发性动脉粥样硬化病变进行的旋切术。对冷冻样本使用抗平滑肌细胞、巨噬细胞、T细胞、中性粒细胞和新蝶呤的抗体进行研究。
在25例UAP患者中的22例中,在冠状动脉罪犯病变部位发现了大量新蝶呤阳性巨噬细胞。然而,在25例SAP患者的病变中,只有11例显示新蝶呤阳性。定量分析显示,UAP患者的新蝶呤阳性巨噬细胞评分显著高于SAP患者(p<0.001)。此外,新蝶呤阳性巨噬细胞评分分别与中性粒细胞或T细胞数量呈显著正相关(中性粒细胞,r = 0.55,p<0.001;T细胞,r = 0.70,p<0.001)。
新蝶呤可被视为人类冠状动脉粥样硬化病变中斑块炎症和不稳定过程的重要因素之一。其在该过程中的确切作用尚需进一步研究。