Chomiki N, Henry M, Alessi M C, Anfosso F, Juhan-Vague I
Laboratory of Hematology, CHU Timone, Marseille, France.
Thromb Haemost. 1994 Jul;72(1):44-53.
Individuals with elevated levels of plasminogen activator inhibitor type 1 are at risk of developing atherosclerosis. The mechanisms leading to increased plasma PAI-1 concentrations are not well understood. The link observed between increased PAI-1 levels and insulin resistance has lead workers to investigate the effects of insulin or triglyceride rich lipoproteins on PAI-1 production by cultured hepatocytes or endothelial cells. However, little is known about the contribution of these cells to PAI-1 production in vivo. We have studied the expression of PAI-1 in human liver sections as well as in vessel walls from different territories, by immunocytochemistry and in situ hybridization. We have observed that normal liver endothelial cells expressed PAI-1 while parenchymal cells did not. However, this fact does not refute the role of parenchymal liver cells in pathological states. In healthy vessels, PAI-1 mRNA and protein were detected primarily at the endothelium from the lumen as well as from the vasa vasorum. In normal arteries, smooth muscle cells were able to produce PAI-1 depending on the territory tested. In deeply altered vessels, PAI-1 expression was observed in neovessels scattering the lesions, in some intimal cells and in smooth muscle cells. Local increase PAI-1 mRNA described in atherosclerotic lesions could be due to the abundant neovascularization present in the lesion as well as a raised expression in smooth muscle cells. The increased PAI-1 in atherosclerosis could lead to fibrin deposit during plaque rupture contributing further to the development and progression of the lesion.
纤溶酶原激活物抑制剂1水平升高的个体有患动脉粥样硬化的风险。导致血浆PAI - 1浓度升高的机制尚不完全清楚。PAI - 1水平升高与胰岛素抵抗之间的关联促使研究人员研究胰岛素或富含甘油三酯的脂蛋白对培养的肝细胞或内皮细胞产生PAI - 1的影响。然而，对于这些细胞在体内PAI - 1产生中的作用知之甚少。我们通过免疫细胞化学和原位杂交研究了PAI - 1在人肝脏切片以及不同部位血管壁中的表达。我们观察到正常肝脏内皮细胞表达PAI - 1，而实质细胞不表达。然而，这一事实并不否定实质肝细胞在病理状态下的作用。在健康血管中，PAI - 1 mRNA和蛋白主要在内皮细胞的管腔以及血管滋养管中被检测到。在正常动脉中，平滑肌细胞能够根据所检测的部位产生PAI - 1。在严重病变的血管中，在散布于病变处的新生血管、一些内膜细胞和平滑肌细胞中观察到PAI - 1表达。动脉粥样硬化病变中描述的局部PAI - 1 mRNA增加可能是由于病变中存在丰富的新生血管以及平滑肌细胞中表达升高所致。动脉粥样硬化中PAI - 1增加可能导致斑块破裂时纤维蛋白沉积，进一步促进病变的发展和进展。
