Factor XI Deficiency Protects Against Atherogenesis in Apolipoprotein E/Factor XI Double Knockout Mice

Arteriosclerosis, Thrombosis, and Vascular Biology
Reut Shnerb GanorOphira Salomon

Abstract

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. 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. FXI deprivation was shown to slow down atherogenesis in mice. The results suggest that the development of atherosclerosis can be prevented by targeting FXI.

References

Jul 1, 1997·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·D T LaskowitzD S Warner
Dec 20, 2002·Nature·Peter Libby
Jul 23, 2003·Journal of Thrombosis and Haemostasis : JTH·O SalomonU Seligsohn
Apr 22, 2005·The New England Journal of Medicine·Göran K Hansson
May 28, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·J Khallou-LaschetA Nicoletti
Dec 31, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·Rachel E TilleyNigel Mackman
May 19, 2006·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·Franca BiloraAntonio Girolami
Aug 2, 2006·American Journal of Clinical Pathology·David T YangGeorge M Rodgers
Sep 23, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Florian BeaErwin Blessing
Jun 2, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Susanne ZadelaarTeake Kooistra
May 22, 2008·The Journal of Infectious Diseases·Erik I TuckerAndrás Gruber
Aug 11, 2010·Circulation·Julian Ilcheff BorissoffHenri M H Spronk
May 6, 2011·The New England Journal of Medicine·Julian Ilcheff BorissoffHugo ten Cate
Jun 23, 2011·Journal of Thrombosis and Haemostasis : JTH·D R FabriV R Arruda
Sep 29, 2011·Journal of Thrombosis and Haemostasis : JTH·Marjan ZwiersK Meijer
Oct 25, 2011·Journal of Thrombosis and Haemostasis : JTH·Mike Makris, J J Van Veen
Nov 15, 2011·The New England Journal of Medicine·Jessica L MegaUNKNOWN ATLAS ACS 2–TIMI 51 Investigators
Dec 17, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Attie TuinenburgRoger E G Schutgens
May 15, 2012·Journal of Thrombosis and Haemostasis : JTH·R LoeffenH ten Cate
Sep 21, 2012·Blood·Thomas RennéCoen Maas
Aug 10, 2013·Seminars in Thrombosis and Hemostasis·Stefano Duga, Ophira Salomon
Jan 5, 2014·Blood·Pieter W Kamphuisen, Hugo ten Cate
Jun 21, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Maurits L van MontfoortJoost C M Meijers
Dec 9, 2014·The New England Journal of Medicine·Harry R BüllerUNKNOWN FXI-ASO TKA Investigators
May 16, 2015·Journal of Thrombosis and Haemostasis : JTH·D GailaniA Gruber
May 29, 2015·Journal of Atherosclerosis and Thrombosis·Kohei Tatsumi, Nigel Mackman
Jul 8, 2015·Journal of Thrombosis and Haemostasis : JTH·T G MastenbroekJ M E M Cosemans

❮ Previous
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Citations

Jun 1, 2018·Journal of Thrombosis and Haemostasis : JTH·B M M KremersH M H Spronk
Jul 28, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Ziad Mallat
May 26, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Wolfram Ruf
Feb 24, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Sravya KattulaAlisa S Wolberg
Feb 26, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Nigel Mackman
May 14, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·David Gailani, Andras Gruber
Aug 18, 2020·Journal of Alzheimer's Disease : JAD·Edin BegicMirsada Causevic
Apr 3, 2018·Haemophilia : the Official Journal of the World Federation of Hemophilia·O SalomonW Saliba
Jan 25, 2018·Blood Advances·Christina U LorentzAndrás Gruber
Jul 27, 2018·Research and Practice in Thrombosis and Haemostasis·Renske H OlieHugo Ten Cate
May 28, 2019·Journal of Thrombosis and Haemostasis : JTH·Bassem M MohammedDavid Gailani
Feb 6, 2017·Science Translational Medicine·Sabine KossmannPhilip Wenzel
Oct 26, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Hong S LuAlan Daugherty
Oct 4, 2017·British Journal of Anaesthesia·E R StraussK A Tanaka

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