FIBRIN D‐DIMER FRAGMENTS ENHANCE INFLAMMATORY RESPONSES IN MACROPHAGES: ROLE IN ADVANCING ATHEROSCLEROSIS
FIBRIN D‐DIMER FRAGMENTS ENHANCE INFLAMMATORY RESPONSES IN MACROPHAGES: ROLE IN ADVANCING ATHEROSCLEROSIS
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DOI：
10.1111/j.1440-1681.2007.04570.x
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发表时间：
2007-03
影响因子：
2.9
通讯作者：
Dong Zhou;Peng Yang;Bin Zhou;Y. Rui
中科院分区：
文献类型：
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作者：
Dong Zhou;Peng Yang;Bin Zhou;Y. Rui
1在人群研究中，凝血酶原D-二聚体被认为是心血管疾病风险的一致和独立的标志物，并且与患者的动脉粥样硬化严重程度相关。然而，纤维蛋白D-二聚体在动脉粥样硬化形成过程中巨噬细胞源性泡沫细胞形成中的作用仍不清楚。2在本研究中，我们使用微阵列技术，通过研究与动脉粥样硬化病理生理过程相关的128个基因的表达水平，确定了100 ng/mL纤维蛋白D-二聚体片段对动脉粥样硬化中巨噬细胞功能的影响。3结果显示，有27个基因被D-二聚体片段增强到对照的两倍以上。这27个基因分属6类，包括粘附分子、细胞外分子、脂质转运和代谢相关分子、细胞生长和增殖分子、转录调节因子和应激反应基因。我们继续使用SYBR真实的时间聚合酶链反应测定其中5个基因（细胞间粘附分子-1、基质金属蛋白酶-9、氧化低密度脂蛋白受体1、血管内皮生长因子A和过氧化物酶体增殖物激活受体α）的表达水平。结果证实了基因上调，类似于用微阵列获得的结果，用D-二聚体处理后。4因此，本研究提供了关于D-二聚体在巨噬细胞功能中的促动脉粥样硬化作用的直接证据，其主要是在巨噬细胞源性泡沫细胞形成期间增强炎症反应。
1 Fibrin D‐dimer is considered a consistent and independent marker of the risk of cardiovascular disease in population studies, as well as being related to atherosclerosis severity in patients. However, the role of fibrin D‐dimer in macrophage‐derived foam cell formation during atherogenesis remains unclear. 2 In the present study, using microarray techniques, we determined the effects of 100 ng/mL fibrin D‐dimer fragments on macrophage cell function in atherosclerosis by investigating the expression levels of 128 genes related to the atherosclerotic pathophysiological processes. 3 The results showed that 27 genes were enhanced by D‐dimer fragments to over twofold of control. These 27 genes belonged to six groups and included adhesion molecules, extracellular molecules, molecules related to lipid transport and metabolism, cell growth and proliferation molecules, transcription regulators and genes responsive to stress. We proceeded to determine the expression levels of five of these genes (intercellular adhesion molecule‐1, matrix metalloproteinase‐9, oxidized low‐density lipoprotein receptor 1, vascular endothelial growth factor A and peroxisome proliferator‐activated receptor α) using SYBR real‐time polymerase chain reaction. The results confirmed gene upregulation, similar to the results obtained with the microarray, following treatment with D‐dimer. 4 Therefore, the present study provides direct evidence regarding the pro‐atherosclerotic role of D‐dimer in macrophage function, which is mainly to enhance the inflammatory response during macrophage‐derived foam cell formation.