Protection against atherogenesis in mice mediated by human apolipoprotein A-IV.
Apolipoproteins are protein constituents of plasma lipid transport particles. Human apolipoprotein A-IV (apoA-IV) was expressed in the liver of C57BL/6 mice and mice deficient in apoE, both of which are prone to atherosclerosis, to investigate whether apoA-IV protects against this disease. In transgenic C57BL/6 mice on an atherogenic diet, the serum concentration of high density lipoprotein (HDL) cholesterol increased by 35 percent, whereas the concentration of endogenous apoA-I decreased by 29 percent, relative to those in transgenic mice on a normal diet. Expression of human apoA-IV in apoE-deficient mice on a normal diet resulted in an even more severe atherogenic lipoprotein profile, without affecting the concentration of HDL cholesterol, than that in nontransgenic apoE-deficient mice. However, transgenic mice of both backgrounds showed a substantial reduction in the size of atherosclerotic lesions. Thus, apoA-IV appears to protect against atherosclerosis by a mechanism that does not involve an increase in HDL cholesterol concentration.
Duverger
N
N
Rhone-Poulenc Rorer, Gencell Division, Atherosclerosis Department, Centre de Recherches de Vitry-Alfortville, 94403 Vitry sur Seine Cedex, France. G. C.
Tremp
G
G
Caillaud
J M
JM
Emmanuel
F
F
Castro
G
G
Fruchart
J C
JC
Steinmetz
A
A
Denèfle
P
P
D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood; D001054:Apolipoproteins A / Q000097:blood / Q000502:physiology*; D001057:Apolipoproteins E / Q000097:blood / Q000172:deficiency; D001161:Arteriosclerosis / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D004036:Diet, Atherogenic; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; C022205:apolipoprotein A-IV; D002784:Cholesterol