Tissue Factor Expression on Macrophages in Coronary Plaques in Patients with Unstable Angina

Abstract

Tissue factor is a membrane-bound glycoprotein that functions in the extrinsic pathway of blood coagulation by acting as a cofactor for factor VII, and the resulting complex leads to thrombin production in vivo. The purpose of the present study is to determine whether macrophages express tissue factor in human coronary atherosclerotic plaques. We examined directional coronary atherectomy specimens from 24 patients with unstable angina and 23 with stable exertional angina. In these specimens, macrophages were detected in 22 (92%) of 24 patients with unstable angina versus 12 (52%) of 23 with stable exertional angina (P = .003). The percentage of macrophage infiltration area was significantly larger in patients with unstable angina than in those with stable exertional angina (17 +/- 3% versus 6 +/- 2%, P = .008). The immunohistochemical double staining revealed the expression of tissue factor on macrophages in 18 (75%) of 24 patients with unstable angina versus 3 (13%) of 23 with stable exertional angina (P < .0001). Thrombus was identified in 20 (83%) of 24 patients with unstable angina versus 12 (52%) of 23 with stable exertional angina (P = .02). Fibrin deposition was mainly observed around macrophages expressing tissue factor in the patients with unstable angina. We have shown that tissue factor expression on macrophages was more frequent in coronary atherosclerotic plaques in patients with unstable angina. Tissue factor expressed on macrophages may play an important role in the thrombogenicity in coronary atherosclerotic plaques of these patients.

Increased plasma thioredoxin in patients with acute myocardial infarction

“…8 We have reported that in directional coronary atherectomy specimens, the area of macrophage infiltration in the sections from patients with unstable angina and AMI was larger than that in patients with SEA, and tissue factor expression on macrophages was more frequently observed in these patients. 9 Therefore, one of the major origins 585 of elevated plasma thioredoxin is speculated to be unstable atheroscrelotic plaques in the infarct-related artery. It was also reported that the appearance of oxidative products in peripheral blood of patients with AMI is the result of their increased release from the infarcted heart during the inflammatory phase of myocardial ischemia.…”

Inflammation and the Development of Atherosclerosis

“…The thrombogenicity of disrupted human atherosclerotic plaque can be predicted by its TF content and activity. Circulating levels of TF are also associated with increased blood thrombogenicity in patients with unstable angina and chronic coronary artery disease 33) and are predictive of outcomes in patients with unstable angina 34) . Specific inhibition of TF by tissue factor pathway inhibitor (TFPI), a circulating, lipoprotein-associated, Kunitz-type protease inhibitor, has been shown to significantly reduce plaque thrombogenicity 35) .…”

Serum Amyloid A Induces Monocyte Tissue Factor

“…Lymphocytes, which do not express TF themselves, are required for optimal TF production by monocytes/macrophages (18). Hypercoagulability associated with vascular disease is considered to be principally mediated by TF expressed within atherosclerotic plaque, and on monocytes in the circulation (20,21), and TF expression is associated with macrophage-mediated fibrin deposition, which is common in most inflammatory lesions (22). In this study, we show a potent and rapid induction of TF activity, mRNA, and protein on normal human monocytes by SAA.…”