Increased Monocyte Adhesion to Aortic Endothelium in Rats With Hyperhomocysteinemia: Role of Chemokine and Adhesion Molecules
Increased Monocyte Adhesion to Aortic Endothelium in Rats With Hyperhomocysteinemia: Role of Chemokine and Adhesion Molecules
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DOI：
10.1161/01.atv.0000035404.18281.37
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发表时间：
2002-11
期刊：
影响因子：
--
通讯作者：
Guoping Wang;C. Woo;F. Sung;Y. Siow;K. O
中科院分区：
文献类型：
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作者：
Guoping Wang;C. Woo;F. Sung;Y. Siow;K. O
目的：同型半胱氨酸(Hcy)在体外对单核细胞趋化蛋白-1(MCP-1)表达的刺激作用在Hcy介导的动脉粥样硬化中起重要作用。我们调查了这种刺激效应是否在体内发生，导致单核细胞与内皮细胞黏附。方法和结果：将SD大鼠分为4组。一组大鼠在高蛋氨酸饮食4周后诱发高同型半胱氨酸血症(血清Hcy水平是对照组的4-5倍)。高同型半胱氨酸血症大鼠主动脉内皮细胞表面ED-1阳性细胞数明显增加。血管内皮细胞MCP-1、血管细胞黏附分子-1(VCAM-1)和E-选择素的表达明显增加。识别MCP-1、VCAM-1或E-选择素的抗体可取消高同型半胱氨酸血症大鼠单核细胞与高同型半胱氨酸血症大鼠主动脉内皮细胞的结合。高同型半胱氨酸血症大鼠血管内皮依赖性舒张功能受损。结论--这些结果表明，在没有其他已知危险因素的情况下，高同型半胱氨酸血症刺激体内MCP-1、VCAM-1和E-选择素的表达，导致单核细胞与主动脉内皮细胞的粘附性增加。这种作用可能通过促进单核/巨噬细胞渗入动脉壁而显著促进动脉粥样硬化的发展。
Objective—The stimulatory effect of homocysteine (Hcy) on monocyte chemoattractant protein (MCP)-1 expression in vitro has been suggested to play an important role in Hcy-mediated atherosclerosis. We investigated whether such a stimulatory effect occurs in vivo, leading to monocyte adhesion to the endothelium. Methods and Results—Sprague-Dawley rats were divided into 4 groups. Hyperhomocysteinemia was induced in 1 group of rats after 4 weeks of a high-methionine diet (serum Hcy levels were 4- to 5-fold higher than levels in control rats). The number of ED-1–positive cells present on the surface of aortic endothelium was significantly elevated in hyperhomocysteinemic rats. There was a significant increase in the expression of MCP-1, vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in the endothelium. Antibodies recognizing MCP-1, VCAM-1, or E-selectin could abolish the enhanced monocyte binding to the aortic endothelium of hyperhomocysteinemic rats. Endothelium-dependent aortic relaxation was impaired in hyperhomocysteinemic rats. Conclusions—These results suggest that in the absence of other known risk factors, hyperhomocysteinemia stimulates the expression of MCP-1, VCAM-1, and E-selectin in vivo, leading to increased monocyte adhesion to the aortic endothelium. Such an effect may contribute significantly to the development of atherosclerosis by facilitating monocyte/macrophage infiltration into the arterial wall.