title: Factor XI Deficiency Protects Against Atherogenesis in Apolipoprotein E/Factor XI Double Knockout Mice.
abstract: OBJECTIVE
  Atherosclerosis and atherothrombosis are still major causes of mortality in the Western world, even after the widespread use of cholesterol-lowering medications. Recently, an association between local thrombin generation and atherosclerotic burden has been reported. Here, we studied the role of factor XI (FXI) deficiency in the process of atherosclerosis in mice.
  
  
  RESULTS
  Apolipoprotein E/FXI double knockout mice, created for the first time in our laboratory. There was no difference in cholesterol levels or lipoprotein profiles between apolipoprotein E knockout and double knockout mice. Nevertheless, in 24-week-old double knockout mice, the atherosclerotic lesion area in the aortic sinus was reduced by 32% (P=0.004) in comparison with apolipoprotein E knockout mice. In 42-week-old double knockout mice, FXI deficiency inhibited atherosclerosis progression significantly in the aortic sinus (25% reduction, P=0.024) and in the aortic arch (49% reduction, P=0.028), with a prominent reduction of macrophage infiltration in the atherosclerotic lesions.
  
  
  CONCLUSIONS
  FXI deprivation was shown to slow down atherogenesis in mice. The results suggest that the development of atherosclerosis can be prevented by targeting FXI.
authors.affiliation: From the The Bert W. Strassburger Lipid Center (R.S.G., D.H., H.L., A.S.) and Department of Pathology (G.S., C.A.), and Thrombosis Unit (R.S.G., I.T., O.S.), Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine (R.S.G., D.H., G.S., H.L., C.A., I.T., O.S.), Tel-Aviv University, Tel-Aviv, Israel; and Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN (D.G.).
authors.forename: Reut
authors.initials: R
authors.lastname: Shnerb Ganor
authors.affiliation: From the The Bert W. Strassburger Lipid Center (R.S.G., D.H., H.L., A.S.) and Department of Pathology (G.S., C.A.), and Thrombosis Unit (R.S.G., I.T., O.S.), Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine (R.S.G., D.H., G.S., H.L., C.A., I.T., O.S.), Tel-Aviv University, Tel-Aviv, Israel; and Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN (D.G.).
authors.forename: Dror
authors.initials: D
authors.lastname: Harats
authors.affiliation: From the The Bert W. Strassburger Lipid Center (R.S.G., D.H., H.L., A.S.) and Department of Pathology (G.S., C.A.), and Thrombosis Unit (R.S.G., I.T., O.S.), Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine (R.S.G., D.H., G.S., H.L., C.A., I.T., O.S.), Tel-Aviv University, Tel-Aviv, Israel; and Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN (D.G.).
authors.forename: Ginette
authors.initials: G
authors.lastname: Schiby
authors.affiliation: From the The Bert W. Strassburger Lipid Center (R.S.G., D.H., H.L., A.S.) and Department of Pathology (G.S., C.A.), and Thrombosis Unit (R.S.G., I.T., O.S.), Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine (R.S.G., D.H., G.S., H.L., C.A., I.T., O.S.), Tel-Aviv University, Tel-Aviv, Israel; and Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN (D.G.).
authors.forename: David
authors.initials: D
authors.lastname: Gailani
authors.affiliation: From the The Bert W. Strassburger Lipid Center (R.S.G., D.H., H.L., A.S.) and Department of Pathology (G.S., C.A.), and Thrombosis Unit (R.S.G., I.T., O.S.), Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine (R.S.G., D.H., G.S., H.L., C.A., I.T., O.S.), Tel-Aviv University, Tel-Aviv, Israel; and Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN (D.G.).
authors.forename: Hanna
authors.initials: H
authors.lastname: Levkovitz
authors.affiliation: From the The Bert W. Strassburger Lipid Center (R.S.G., D.H., H.L., A.S.) and Department of Pathology (G.S., C.A.), and Thrombosis Unit (R.S.G., I.T., O.S.), Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine (R.S.G., D.H., G.S., H.L., C.A., I.T., O.S.), Tel-Aviv University, Tel-Aviv, Israel; and Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN (D.G.).
authors.forename: Camila
authors.initials: C
authors.lastname: Avivi
authors.affiliation: From the The Bert W. Strassburger Lipid Center (R.S.G., D.H., H.L., A.S.) and Department of Pathology (G.S., C.A.), and Thrombosis Unit (R.S.G., I.T., O.S.), Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine (R.S.G., D.H., G.S., H.L., C.A., I.T., O.S.), Tel-Aviv University, Tel-Aviv, Israel; and Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN (D.G.).
authors.forename: Ilia
authors.initials: I
authors.lastname: Tamarin
authors.affiliation: From the The Bert W. Strassburger Lipid Center (R.S.G., D.H., H.L., A.S.) and Department of Pathology (G.S., C.A.), and Thrombosis Unit (R.S.G., I.T., O.S.), Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine (R.S.G., D.H., G.S., H.L., C.A., I.T., O.S.), Tel-Aviv University, Tel-Aviv, Israel; and Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN (D.G.).
authors.forename: Aviv
authors.initials: A
authors.lastname: Shaish
authors.affiliation: From the The Bert W. Strassburger Lipid Center (R.S.G., D.H., H.L., A.S.) and Department of Pathology (G.S., C.A.), and Thrombosis Unit (R.S.G., I.T., O.S.), Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine (R.S.G., D.H., G.S., H.L., C.A., I.T., O.S.), Tel-Aviv University, Tel-Aviv, Israel; and Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN (D.G.). ophiras@sheba.health.gov.il.
authors.forename: Ophira
authors.initials: O
authors.lastname: Salomon
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D005172:Factor XI / Q000235:genetics / Q000378:metabolism*; D005173:Factor XI Deficiency / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D008077:Lipoproteins, LDL / Q000097:blood; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D058226:Plaque, Atherosclerotic
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D008077:Lipoproteins, LDL; D005172:Factor XI; D002784:Cholesterol
keywords: atherosclerosis; factor XI