title: Procoagulant activity expression by macrophages from atheromatous vascular plaques.
abstract: Embolization of thrombi from ulcerated plaques is an important cause of morbidity from atherosclerotic carotid artery disease. Factors controlling thrombus formation on these lesions are not well understood. Macrophages were isolated from atherosclerotic plaques to assess their potential to promote local fibrin deposition. Plaques were collected from 11 patients undergoing carotid endarterectomy and 9 patients undergoing reconstructive procedures for atherosclerotic disease of their distal aorta or femoral arteries. Blood was also collected concurrently to isolate monocytes. Procoagulant activity (PCA) of carotid macrophages (8.6 +/- 4.1 mU/10(6) cells) was significantly higher than that of macrophages from non-carotid lesions (0.35 +/- 0.20 mU/10(6) cells; P less than 0.05) or blood monocytes from either group of patients. The PCA of carotid plaque macrophages from patients with recent emboli was 16.1 +/- 8.4 mU/10(6) cells (n = 5) compared to 2.4 +/- 0.8 mU/10(6) cells (n = 6) for plaque macrophages from assymptomatic carotid endarterectomy patients. Carotid macrophage PCA was factor V and factor VII dependent. Its functional activity was inhibited by an anti-tissue factor antibody, and immunohistochemical studies on tissue sections from carotid plaques showed tissue factor in areas where macrophages were abundant. These studies demonstrate that macrophages within carotid artery plaques have augmented procoagulant activity compared with blood monocytes and macrophages from other atherosclerotic lesions and indicate that carotid plaque macrophages are activated. Augmented macrophage PCA may contribute to thrombus formation on ulcerated plaques.
authors.affiliation: Monash University Department of Medicine, Prince Henry's Hospital, Melbourne, Australia.
authors.forename: P G
authors.initials: PG
authors.lastname: Tipping
authors.forename: J
authors.initials: J
authors.lastname: Malliaros
authors.forename: S R
authors.initials: SR
authors.lastname: Holdsworth
mesh_terms: D001011:Aorta / Q000473:pathology; D001161:Arteriosclerosis / Q000378:metabolism*; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000378:metabolism*; D002340:Carotid Artery Diseases / Q000378:metabolism*; D005263:Femoral Artery / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008264:Macrophages / Q000378:metabolism*
chemical_list: D001779:Blood Coagulation Factors; C045072:macrophage procoagulant activity