Iso Yoshitaka, Suzuki Hiroshi, Sato Takatoshi, Shoji Makoto, Shibata Masayuki, Hamazaki Yuji, Koba Shinji, Sakai Tetsuo, Murakami Mikitaka, Geshi Eiichi, Katagiri Takashi
Third Department of Internal Medicine, Showa University School of Medicine, Hatanodai 1-5-8, Shinagawa-ku, Tokyo 142-8666.
J Cardiol. 2003 Jul;42(1):29-36.
Primary coronary atherosclerotic lesions(de novo lesions) are a type of inflammatory vascular disease. Restenotic lesions after percutaneous coronary intervention mainly consist of proliferative vascular smooth muscle cells. Recent studies have demonstrated that locally synthesized cytokines, including chemokines, are important in both these coronary lesions. Monocyte chemoattractant protein(MCP)-1 and macrophage colony-stimulating factor(M-CSF) are two of the associated chemokines, but their role in coronary artery disease has not been sufficiently clarified. This study investigated the expression of MCP-1 and c-fms/M-CSF receptor in human coronary tissues.
Histological and immunohistochemical studies used samples obtained from patients who underwent directional coronary atherectomy(28 de novo lesions and 16 restenotic lesions). The following primary antibodies were used: anti-MCP-1, anti-c-fms, anti-macrophages and anti-alpha-smooth muscle actin.
Focal accumulation of macrophage-derived foam cells, thrombus, cholesterol clefts and calcification tended to be more frequent in de novo lesions than in restenotic lesions. On the other hand, restenotic lesions mainly consisted of stellate vascular smooth muscle cells and extracellular matrix. The expression of MCP-1-positive cells almost coincided with the macrophages. In contrast, staining for MCP-1 was little seen in the stellate vascular smooth muscle cells. Expression of c-fms was found in both macrophages and stellate vascular smooth muscle cells. Expression patterns of MCP-1 and c-fms exhibited no difference between the two lesion types.
Both MCP-1 and the M-CSF/c-fms system are involved in the atherogenesis of de novo lesions. However, the M-CSF/c-fms system, rather than MCP-1, is more important in the late stage of restenosis.
原发性冠状动脉粥样硬化病变(新生病变)是一种炎症性血管疾病。经皮冠状动脉介入术后的再狭窄病变主要由增殖的血管平滑肌细胞组成。最近的研究表明,包括趋化因子在内的局部合成细胞因子在这两种冠状动脉病变中均起重要作用。单核细胞趋化蛋白-1(MCP-1)和巨噬细胞集落刺激因子(M-CSF)是两种相关的趋化因子,但它们在冠状动脉疾病中的作用尚未得到充分阐明。本研究调查了人冠状动脉组织中MCP-1和c-fms/M-CSF受体的表达情况。
组织学和免疫组织化学研究使用了从接受定向冠状动脉斑块旋切术的患者获取的样本(28例新生病变和16例再狭窄病变)。使用了以下一抗:抗MCP-1、抗c-fms、抗巨噬细胞和抗α-平滑肌肌动蛋白。
巨噬细胞源性泡沫细胞、血栓、胆固醇裂隙和钙化的局灶性积聚在新生病变中比在再狭窄病变中更常见。另一方面,再狭窄病变主要由星状血管平滑肌细胞和细胞外基质组成。MCP-1阳性细胞的表达几乎与巨噬细胞一致。相比之下,在星状血管平滑肌细胞中很少见到MCP-1染色。在巨噬细胞和星状血管平滑肌细胞中均发现了c-fms的表达。MCP-1和c-fms的表达模式在两种病变类型之间没有差异。
MCP-1和M-CSF/c-fms系统均参与新生病变的动脉粥样硬化形成。然而,M-CSF/c-fms系统而非MCP-1在再狭窄的后期更为重要。