title: Early atherosclerosis exhibits an enhanced procoagulant state.
abstract: BACKGROUND
  Thrombin generation in vivo may be important in regulating atherosclerotic progression. In the present study, we examined for the first time the activity and presence of relevant coagulation proteins in relation to the progression of atherosclerosis.
  
  
  RESULTS
  Both early and stable advanced atherosclerotic lesions were collected pairwise from each individual (n=27) during autopsy. Tissue homogenates were prepared from both total plaques and isolated plaque layers, in which the activity of factors (F) II, X, and XII and tissue factor was determined. Microarray analysis was implemented to elucidate local messenger RNA synthesis of coagulation proteins. Part of each specimen was paraffin embedded, and histological sections were immunohistochemically stained for multiple coagulation markers with the use of commercial antibodies. Data are expressed as median (interquartile range [IQR]). Tissue factor, FII, FX, and FXII activities were significantly higher in early atherosclerotic lesions than in stable advanced atherosclerotic lesions. Endogenous thrombin potential and thrombin-antithrombin complex values consolidated a procoagulant profile of early atherosclerotic lesions (endogenous thrombin potential, 1240 nmol/L x min [IQR, 1173 to 1311]; thrombin-antithrombin complex, 1045 ng/mg [IQR, 842.6 to 1376]) versus stable advanced atherosclerotic lesions (endogenous thrombin potential, 782 nmol/L x min [IQR, 0 to 1151]; thrombin-antithrombin complex, 718.4 ng/mg [IQR, 508.6 to 1151]). Tissue factor, FVII, and FX colocalized with macrophages and smooth muscle cells. In addition, multiple procoagulant and anticoagulant proteases were immunohistochemically mapped to various locations throughout the atherosclerotic vessel wall in both early and advanced atherosclerotic stages.
  
  
  CONCLUSIONS
  This study shows an enhanced procoagulant state of early-stage atherosclerotic plaques compared with advanced-stage plaques, which may provide novel insights into the role of coagulation during atherosclerotic plaque progression.
authors.affiliation: Laboratory for Clinical Thrombosis and Hemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Universiteitsingel 50, PO Box 616, Box 8, 6200 MD Maastricht, the Netherlands. j.ilcheff@maastrichtuniversity.nl
authors.forename: Julian Ilcheff
authors.initials: JI
authors.lastname: Borissoff
authors.forename: Sylvia
authors.initials: S
authors.lastname: Heeneman
authors.forename: Evren
authors.initials: E
authors.lastname: Kilinç
authors.forename: Peter
authors.initials: P
authors.lastname: Kassák
authors.forename: René
authors.initials: R
authors.lastname: Van Oerle
authors.forename: Kristien
authors.initials: K
authors.lastname: Winckers
authors.forename: José W P
authors.initials: JW
authors.lastname: Govers-Riemslag
authors.forename: Karly
authors.initials: K
authors.lastname: Hamulyák
authors.forename: Tilman M
authors.initials: TM
authors.lastname: Hackeng
authors.forename: Mat J A P
authors.initials: MJ
authors.lastname: Daemen
authors.forename: Hugo
authors.initials: H
authors.lastname: ten Cate
authors.forename: Henri M H
authors.initials: HM
authors.lastname: Spronk
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000097:blood*; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000032:analysis*; D005167:Factor VII / Q000032:analysis; D005170:Factor X / Q000032:analysis; D005174:Factor XII / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008074:Lipoproteins / Q000032:analysis; D008297:Male; D008875:Middle Aged; D013917:Thrombin / Q000096:biosynthesis; D013925:Thromboplastin / Q000032:analysis
chemical_list: D001779:Blood Coagulation Factors; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D005167:Factor VII; D005170:Factor X; D005174:Factor XII; D013925:Thromboplastin; D013917:Thrombin