title: Hyperhomocysteinemia independently causes and promotes atherosclerosis in LDL receptor-deficient mice.
abstract: BACKGROUND
  Hyperhomocysteine is an independent risk factor of coronary heart disease (CHD). However, whether hyperhomocysteine affects the progression of atherosclerosis is unclear. In the present study, we examined the effect of hyperhomocysteine on the formation of atherosclerosis in low-density lipoprotein receptor-deficient (LDLr(-/-)) mice.
  
  
  METHODS
  Forty-eight 7-week-old LDLr(-/-) mice were assigned to the following groups: mice fed a standard rodent diet (control group), mice fed a high-methionine diet (high-methionine group), mice fed a high-fat diet (high-fat group), and mice fed a diet high in both methionine and fat (high-methionine and high-fat group). At the age of 19, 23, and 27 weeks, four mice at each interval in every group were sacrificed.
  
  
  RESULTS
  At the end of the study, mice did not show atherosclerotic lesions in the aortic sinus and aortic surface until 27 weeks old in the control group. However, atherosclerotic lesions developed in the other three groups at 19 weeks. The amount of atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group (P < 0.001). Atherosclerotic lesions on the aortic surface in the high-methionine and high-fat group were the most severe. The mean area of atherosclerotic lesions in the aortic sinus compared with atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group (P < 0.001). Atherosclerotic lesions in the aortic sinus in the high-methionine and high-fat group were the most severe.
  
  
  CONCLUSIONS
  Homocysteinemia accelerates atherosclerotic lesions and induces early atherosclerosis independently in LDLr(-/-) mice. Reducing the level of homocysteinemia may be beneficial for prevention and treatment of CHD.
authors.affiliation: Department of Cardiology, Shaoxing Hospital of Zhejiang University, Shaoxing 312000, Zhejiang Province, China.
authors.forename: Hang-Yuan
authors.initials: HY
authors.lastname: Guo
authors.affiliation: Department of Cardiology, Shaoxing Hospital of Zhejiang University, Shaoxing 312000, Zhejiang Province, China.
authors.forename: Fu-Kang
authors.initials: FK
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Shaoxing Hospital of Zhejiang University, Shaoxing 312000, Zhejiang Province, China.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Lv
authors.affiliation: Department of Cardiology, Shaoxing Hospital of Zhejiang University, Shaoxing 312000, Zhejiang Province, China.
authors.forename: Long-Bin
authors.initials: LB
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Shaoxing Hospital of Zhejiang University, Shaoxing 312000, Zhejiang Province, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ji
authors.affiliation: Department of Cardiology, Shaoxing Hospital of Zhejiang University, Shaoxing 312000, Zhejiang Province, China.
authors.forename: Xiao-Ya
authors.initials: XY
authors.lastname: Zhai
authors.affiliation: Department of Cardiology, Shaoxing Hospital of Zhejiang University, Shaoxing 312000, Zhejiang Province, China.
authors.forename: Wei-Liang
authors.initials: WL
authors.lastname: Tang
authors.affiliation: Department of Cardiology, Shaoxing Hospital of Zhejiang University, Shaoxing 312000, Zhejiang Province, China.
authors.forename: Ju-Fang
authors.initials: JF
authors.lastname: Chi
keywords: Atherosclerosis; Homocysteine; Hyperhomocysteinemia; Low-density lipoprotein
references.citation: Circulation. 2006 Feb 14;113(6):791-8
references.pmid: 16461820
references.citation: Annu Rev Nutr. 1999;19:217-46
references.pmid: 10448523
references.citation: Arch Intern Med. 2000 Feb 28;160(4):422-34
references.pmid: 10695683
references.citation: Atherosclerosis. 2006 Feb;184(2):295-301
references.pmid: 16005008
references.citation: Arterioscler Thromb Vasc Biol. 2001 Sep;21(9):1470-6
references.pmid: 11557674
references.citation: J Clin Invest. 2001 Mar;107(6):675-83
references.pmid: 11254667
references.citation: N Engl J Med. 1997 Jul 24;337(4):230-6
references.pmid: 9227928
references.citation: Am J Med. 2009 Jan;122(1 Suppl):S3-S14
references.pmid: 19110086
references.citation: JAMA. 2001 May 16;285(19):2486-97
references.pmid: 11368702
references.citation: Indian J Med Res. 2009 Mar;129(3):279-84
references.pmid: 19491420
references.citation: Cardiovasc Ther. 2010 Apr;28(2):70-9
references.pmid: 20398095
references.citation: JAMA. 1995 Oct 4;274(13):1049-57
references.pmid: 7563456
references.citation: Am J Med. 2001 Apr 16;110 Suppl 6A:3S-11S
references.pmid: 11311191
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15089-94
references.pmid: 14657334
references.citation: Free Radic Biol Med. 2006 Nov 15;41(10):1566-77
references.pmid: 17045925
references.citation: Blood. 2003 May 15;101(10):3901-7
references.pmid: 12506016
references.citation: Am J Pathol. 1969 Jul;56(1):111-28
references.pmid: 5792556
references.citation: J Am Coll Cardiol. 2007 Aug 14;50(7):e1-e157
references.pmid: 17692738
references.citation: Med Pregl. 2009;62 Suppl 3:7-14
references.pmid: 19702110
references.citation: Nat Med. 1996 Apr;2(4):386-9
references.pmid: 8597939