Abstract:
:We have previously generated transgenic (Tg) mice expressing the human apolipoprotein (apo) A-I/C-III/A-IV gene cluster. This expression induced hyperlipidemia but reduced atherosclerotic lesions in genetically modified mice lacking apoE. Atherosclerosis is a multifactorial process and environmental factors such as diet play significant roles in its development. We examined here how an atherogenic diet influences the expression of the human genes and the characteristics of the Tg mice. Our results indicate that a high fat-high cholesterol diet up-regulates the intestinal expression of the three genes and the concentration of the three proteins in plasma. Cholesterol concentration was highly increased in the non-high density lipoprotein (HDL) fraction, and less, although significantly, in the HDL fraction. Tgs showed a 65% reduction in diet-induced aortic lesions compared with non-Tg mice. Atherogenic diet increases the expression of the genes encoding the scavenger receptor class B type I (SR-BI) and ATP binding cassette transporter 1 (ABCA1) proteins. As cholesterol efflux mediated by SR-BI or by ABCA1 was enhanced in Tg mice fed an atherogenic diet, we can hypothesize that increased reverse cholesterol transport is the basis of the protective mechanism observed in these animals. In conclusion, we present evidence that the expression of the human gene cluster in mice protects against atherogenesis in response to an atherogenic diet.
journal_name
FEBS Lettjournal_title
FEBS lettersauthors
Baroukh N,Ostos MA,Vergnes L,Recalde D,Staels B,Fruchart J,Ochoa A,Castro G,Zakin MMdoi
10.1016/s0014-5793(01)02621-7keywords:
subject
Has Abstractpub_date
2001-07-27 00:00:00pages
16-20issue
1-2eissn
0014-5793issn
1873-3468pii
S0014579301026217journal_volume
502pub_type
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