Plasminogen deficiency accelerates vessel wall disease in mice predisposed to atherosclerosis.
Plasminogen deficiency accelerates vessel wall disease in mice predisposed to atherosclerosis.
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DOI：
10.1073/pnas.94.19.10335
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发表时间：
1997-09
影响因子：
11.1
通讯作者：
Q. Xiao;M. J. Danton;D. Witte;M. Kowala;M. Valentine;T. Bugge;J. Degen
中科院分区：
文献类型：
--
作者：
Q. Xiao;M. J. Danton;D. Witte;M. Kowala;M. Valentine;T. Bugge;J. Degen
止血因子和动脉粥样硬化之间的关键联系已经从各种间接观察中推断出来，包括动脉粥样硬化血管内促凝血和纤溶因子的表达，内膜病变中纤维蛋白的存在，以及导致其并入发展中斑块的壁血栓的细胞浸润。为了直接检测关键的纤溶因子纤溶酶原在动脉粥样硬化形成中的作用，将纤溶酶原缺陷小鼠与易患动脉粥样硬化的高胆固醇血症、载脂蛋白E缺陷小鼠杂交。我们报告，纤溶酶原的损失大大加速了载脂蛋白E缺乏动物内膜病变的形成，而纤溶酶原缺乏单独不会引起明显的动脉粥样硬化。这些研究提供了直接证据，表明循环止血因子在脂质代谢紊乱的背景下强烈影响血管壁疾病。
A critical link between hemostatic factors and atherosclerosis has been inferred from a variety of indirect observations, including the expression of procoagulant and fibrinolytic factors within atherosclerotic vessels, the presence of fibrin in intimal lesions, and the cellular infiltration of mural thrombi leading to their incorporation into developing plaques. To directly examine the role of the key fibrinolytic factor, plasminogen, in atherogenesis, plasminogen-deficient mice were crossed to hypercholesterolemic, apolipoprotein E-deficient mice predisposed to atherosclerosis. We report that the loss of plasminogen greatly accelerates the formation of intimal lesions in apolipoprotein E-deficient animals, whereas plasminogen deficiency alone does not cause appreciable atherosclerosis. These studies provide direct evidence that circulating hemostatic factors strongly influence vessel wall disease in the context of a disorder in lipid metabolism.