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Prepublished online as a Blood First Edition Paper on December 27, 2002; DOI 10.1182/blood-2002-08-2606. This Article Full Text (PDF) All Versions of this Article: 2002-08-2606v1 101/10/3901    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wang, H. Articles by Schafer, A. I Search for Related Content PubMed PubMed Citation Articles by Wang, H. Articles by Schafer, A. I Social Bookmarking                   What's this? Submitted August 26, 2002 Accepted December 17, 2002 Hyperhomocysteinemia accelerates atherosclerosis in cystathionine -synthase and apolipoprotein E double knockout mice with and without dietary perturbation Hong Wang*, XiaoHua Jiang, Fan Yang, John W Gaubatz, Lang Ma, Mark J Magera, XiaoFeng Yang, Peter B Berger, William Durante, Henry J Pownall, and Andrew I Schafer Department of Medicine, Baylor College of Medicine, Houston, TX, USA Department of Pharmacology, Baylor College of Medicine, Houston, TX, USA Department of Pathology, Baylor College of Medicine, Houston, TX, USA VA Medical Center, Houston, TX, USA Mayo Clinic, Rochester, MN, USA * Corresponding author; email: hongw{at}bcm.tmc.edu. Although hyperhomocysteinemia is as an independent risk factor for cardiovascular disease, a direct role for homocysteine (Hcy) in this disease remains to be shown. Whereas diet-induced hyperhomocysteinemia promotes atherosclerosis in animal models, the effects of Hcy on atherogenesis in the absence of dietary perturbations is not known. We have generated double knockout mice with targeted deletions of the genes for apolipoprotein E (apoE) and cystathionine -synthase (CBS), which converts Hcy to cystathionine. ApoE-/-/CBS-/- mice developed aortic lesions even in the absence of dietary manipulation; lesion area and lesion cholesteryl ester (CE) and triglyceride (TG) contents increased with animal age and plasma Hcy levels. Plasma total cholesterol was significantly increased, whereas, HDL-cholesterol and TG concentrations of apoE-/-/CBS-/- mice were decreased. Cholesterol esterification and activities of enzymes catalyzing CE or TG formation in the vessel wall and in peritoneal macrophages were not changed by hyperhomocysteinemia. However, uptake of human acetyl-LDL, but not native-LDL, by mouse peritoneal macrophages was higher in the presence of hyperhomocysteinemia. These results suggest that isolated hyperhomocysteinemia is atherogenic, and alters hepatic and macrophage lipoprotein metabolism, in part, by enhancing uptake of modified-LDL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Zhang, X. Jiang, P. Fang, Y. Yan, J. Song, S. Gupta, A. I. Schafer, W. Durante, W. D. Kruger, X. Yang, et al. Hyperhomocysteinemia Promotes Inflammatory Monocyte Generation and Accelerates Atherosclerosis in Transgenic Cystathionine {beta}-Synthase-Deficient Mice Circulation, November 10, 2009; 120(19): 1893 - 1902. [Abstract] [Full Text] [PDF] H. Wu, R. M. Gower, H. Wang, X.-Y. D. Perrard, R. Ma, D. C. Bullard, A. R. Burns, A. Paul, C. W. Smith, S. I. Simon, et al. 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