Enhanced atherothrombotic formation after oxidative injury by FeCl3 to the common carotid artery in severe combined hyperlipidemic mice |
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Authors: | Xunde Xian Yu Ding Yanan Wang Colin Ross Xuming Deng George Liu |
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Affiliation: | a Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China b College of Animal Science and Veterinary Medicine, Jilin University, Changchun, Jilin 130062, China c Department of Pathology, Peking University Health Science Center, Beijing, China d Department of Medical Genetics, University of British Columbia, Centre for Molecular Medicine and Therapeutics, Vancouver, Canada e Department of Molecular Genetics, UT Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390-9046, USA |
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Abstract: | Enhanced susceptibility to atherosclerosis from severe hypertriglyceridemia (HTG) resulting from lipoprotein lipase (LPL) deficiency has been demonstrated in our recent findings which employed a unique mouse model. In the present study we provide further evidence that severe HTG due to LPL deficiency also promotes an atherothrombotic response to arterial injury induced by ferric chloride in a severe combined hyperlipidemic mouse model. Methods and results: A mouse model (LPL−/−XApoE−/− double knockout, DKO) with severe combined hyperlipidemia was established by crossing ApoE and LPL-deficient mice. The common carotid arteries of ApoE knockout (EKO) and DKO mice were subjected to injury by ferric chloride, and the formation of arterial thrombosis together with various markers were compared in these lesions. DKO mice demonstrated significantly enhanced thrombus formation overlying atherosclerotic plaque after injury, which contained smooth muscle cells, macrophages, and neutral lipid. The area of neointima, mean intima/media ratios, and the percentage of luminal stenosis were significantly greater (P < 0.01) in DKO mice. Compared with EKO mice, the expression of von Willebrand factor (vWF) and plasminogen activator inhibitor type 1 (PAI-1) were increased in DKO mice. Conclusions: Severe combined hyperlipidemia promotes thrombosis after ferric chloride injury to atherosclerotic vessels and HTG plays a major role in the process. |
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Keywords: | Lipoprotein lipase (LPL) Hypertriglyceridemia Lipoproteins Carotid artery Thrombosis |
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