Human apolipoprotein A-I gene expression increases high density lipoprotein and suppresses atherosclerosis in the apolipoprotein E-deficient mouse.
Atherosclerosis is a complex disease with both genetic and environmental determinants. Apolipoprotein (Apo) E-deficient mice have been created that are highly susceptible to atherosclerosis. In order to assess the role of human apolipoprotein (hApo) A-I and high density lipoprotein (HDL) in atherosclerosis susceptibility, transgenic mice overexpressing the hApo A-I gene were crossed with Apo E-deficient mice. Apo E-/-, hApo A-I mice with two-fold elevation in HDL cholesterol have markedly diminished atherosclerosis with less fibroproliferative lesions by 8 months of age. A strong reciprocal relationship between HDL cholesterol levels and atherosclerosis was found with HDL levels accounting for 78% of the observed variance in mean lesion area. The effect of HDL on atherosclerosis resistance was independent of non-HDL cholesterol.
Plump
A S
AS
Rockefeller University, New York, NY 10021.
Scott
C J
CJ
Breslow
J L
JL
D000375:Aging / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000254:growth & development / Q000473:pathology; D016632:Apolipoprotein A-I / Q000096:biosynthesis*; D001057:Apolipoproteins E / Q000172:deficiency*; D001161:Arteriosclerosis / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003433:Crosses, Genetic; D015870:Gene Expression; D006801:Humans; D008077:Lipoproteins, LDL / Q000096:biosynthesis* / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000254:growth & development / Q000473:pathology
D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008077:Lipoproteins, LDL; D002784:Cholesterol