Co-localization of tissue factor and tissue factor pathway inhibitor in coronary atherosclerosis

Abstract

Tissue factor (TF) initiates the extrinsic pathway of blood coagulation by acting as a cofactor for Factor VII. Inhibition of the Factor VIIa-TF complex is mediated by the tissue factor pathway inhibitor (TFPI), which is a serine protease inhibitor with three Kunitz-type domains. The localization of TF and TFPI protein has been examined immunohistochemically in various atherosclerotic lesions of coronary arteries from 22 autopsy cases and their messenger RNA expression has been confirmed by reverse transcription-polymerase chain reaction. Four types of atherosclerotic lesion (types I, II, III, and IV) were classified according to the method described by Stary et al. TF and TFPI were localized in endothelial cells, macrophages, macrophage-derived foam cells, and smooth muscle cells in the intimal lesions, medial smooth muscle cells, and endothelial cells of the microvessels in the adventitia. Immunohistochemical double staining revealed the co-localization of TF and TFPI in the endothelial cells and macrophages in four types of atherosclerotic lesions. In type III and IV lesions, the number of TF- and TFPI-positive cells was increased, accompanied by extracellular localization of TF and TFPI in the lipid core of atherosclerotic plaques. Fibrin deposition was found around TF- and TFPI-positive macrophages and in the lipid core of atherosclerotic plaques. TF and TFPI messenger RNA were detected more frequently in coronary arteries with type III and IV lesions than in those with type I and II lesions. The co-localization of TF and TFPI was demonstrated in various atherosclerotic lesions of coronary arteries and was shown to be intimately related to fibrin deposition in advanced atherosclerotic plaques. The co-localization of TF and TFPI may thus be closely associated with thrombogenicity in atherosclerotic lesions of coronary arteries.