Localization and activity of tissue factor in human aortic atherosclerotic lesions

• Published in: Atherosclerosis Vol. 133; no. 2; pp. 213 - 219
• Main Authors: Hatakeyama, Kinta, Asada, Yujiro, Marutsuka, Kousuke, Sato, Yuichiro, Kamikubo, Yuichi, Sumiyoshi, Akinobu
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.09.1997; Elsevier
• Subjects: Adolescent; Adult; Aged; Antigens - chemistry; Aorta, Thoracic - chemistry; Aorta, Thoracic - physiopathology; Arteriosclerosis - immunology; Arteriosclerosis - pathology; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Biotin - metabolism; Blood and lymphatic vessels; Cardiology. Vascular system; Chromogenic Compounds - analysis; Factor VIIa - chemistry; Factor VIIa - metabolism; Factor X - analysis; Factor X - metabolism; Female; Humans; Immunohistochemistry; Male; Medical sciences; Middle Aged; Protein Binding; Thromboplastin - chemistry; Thromboplastin - immunology; Thromboplastin - physiology; Tissue factor; Immunohistochemistry; Tissue factor; Atherosclerosis; Vascular disease; Thoracic aorta; Human; Pathology; Autopsy; Cardiovascular disease; Exploration; Localization
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/S0021-9150(97)00132-9

Tissue factor (TF) is a transmembrane protein that serves as the major initiator of the blood coagulation cascade. The overexpression of TF antigen and mRNA has previously been reported in advanced atherosclerotic lesions. Recently TF procoagulant activity has also been identified in these lesions. However, localization and activity of TF in various stages of atherosclerosis have not yet been reported. We studied TF localization and its activity in three stages of the human atherosclerotic lesions (diffuse intimal thickening, fatty streak, and atheromatous plaque). The thoracic aortas were obtained from 23 autopsy cases and were examined immunohistochemically using an anti-human TF polyclonal antibody and biotinylated factor VIIa (FVIIa) as a probe to test the FVIIa-binding ability of TF. In addition, the TF-mediated activation of factor X (FX) was quantitatively assessed using a chromogenic assay. In lesions of the diffuse intimal thickening and the fatty streak, almost all of intimal smooth muscle cells (SMCs), macrophages, and endothelial cells were positive for TF. In the atheromatous plaques, TF antigen was detected extensively in the extracellular matrix as well as in the intimal cells. TF in all stages of atherosclerotic lesions had the ability to bind biotinylated FVIIa. TF activity was detected in each lesion and was more prominent in fatty streaks and atheromatous plaques than in the diffuse intimal thickening. These results indicate that active TF is expressed in the early stage of atherosclerotic lesions as well as in the advanced stage, and it contributes to the thrombotic property of human atherosclerotic lesions.