Cholesteryl ester transfer protein (CETP) expression protects against diet induced atherosclerosis in SR-BI deficient mice

被引:43
作者
Harder, Christopher
Lau, Paulina
Meng, Andrew
Whitman, Stewart C.
McPherson, Ruth
机构
[1] Univ Ottawa, Inst Heart, Lipoprot & Atherosclerosis Res Grp, Ottawa, ON K1Y 4W7, Canada
[2] Univ Ottawa, Inst Heart, Div Cardiol, Ottawa, ON K1Y 4W7, Canada
关键词
CETP; SR-BI; atherosclerosis; HDL;
D O I
10.1161/01.ATV.0000259357.42089.dc
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective - To determine whether expression of the human CETP transgene protects against diet-induced atherosclerosis in SR-BI deficient mice. Methods and Results - SR-BI deficient (-/-) mice were crossed with CETP transgenic (CETPtg) mice to produce a colony of SR-BI-/- x CETPtg mice in a C57B1/6 background. Age and sex matched groups of genetically modified and wild-type C57B1/6 mice were fed a high fat, high cholesterol diet for 22 weeks. In both wild-type and SR-BI-/- mice, expression of the CETP transgene reduced the cholesterol content and increased the density of lipoprotein particles in the HDL density range. In SR-BI-/- x CETPtg mice, CETP activity inversely correlated with total plasma cholesterol levels and shifted the buoyant HDL typical of SR-BI deficiency toward a more normal density HDL particle. Atherosclerosis at the level of the aortic arch was evident in both male and female SR-BI deficient mice but occurred to a greater extent in the females. Expression of CETP markedly attenuated the development of atherosclerosis in SR-BI deficient mice fed an atherogenic diet (P < 0.003). Conclusions - Expression of the human CETP transgene protects SR-BI deficient mice from atherosclerosis, consistent with a role for CETP in remodeling HDL and providing an alternative pathway for the selective uptake of HDL-CE by the liver.
引用
收藏
页码:858 / 864
页数:7
相关论文
共 42 条
  • [1] Cholesteryl ester transfer protein mediates selective uptake of high density lipoprotein cholesteryl esters by human adipose tissue
    Benoist, F
    Lau, P
    McDonnell, M
    Doelle, H
    Milne, R
    McPherson, R
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (38) : 23572 - 23577
  • [2] BLIGH EG, 1959, CAN J BIOCHEM PHYS, V37, P911
  • [3] Bruce C, 1998, J LIPID RES, V39, P1071
  • [4] Scavenger receptor class B type I mediates the selective uptake of high-density lipoprotein-associated cholesteryl ester by the liver in mice
    Brundert, M
    Ewert, A
    Heeren, J
    Behrendt, B
    Ramakrishnan, R
    Greten, H
    Merkel, M
    Rinninger, F
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2005, 25 (01) : 143 - 148
  • [5] CALVO D, 1993, J BIOL CHEM, V268, P18929
  • [6] CAMUS MC, 1983, J LIPID RES, V24, P1210
  • [7] Cholesteryl ester transfer protein corrects dysfunctional high density lipoproteins and reduces aortic atherosclerosis in lecithin cholesterol acyltransferase transgenic mice
    Föger, B
    Chase, M
    Amar, MJ
    Vaisman, BL
    Shamburek, RD
    Paigen, B
    Furchart-Najib, J
    Paiz, JA
    Koch, CA
    Hoyt, RF
    Brewer, HB
    Santamarina-Fojo, S
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (52) : 36912 - 36920
  • [8] Increasing high-density lipoprotein cholesterol in dyslipidemia by cholesteryl ester transfer protein inhibition - An update for clinicians
    Forrester, JS
    Makkar, R
    Shah, PK
    [J]. CIRCULATION, 2005, 111 (14) : 1847 - 1854
  • [9] Cholesteryl ester transfer protein directly mediates selective uptake of high density lipoprotein cholesteryl esters by the liver
    Gauthier, A
    Lau, P
    Zha, XH
    Milne, R
    McPherson, R
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2005, 25 (10) : 2177 - 2184
  • [10] Diet and murine atherosclerosis
    Getz, GS
    Reardon, CA
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2006, 26 (02) : 242 - 249