Inhibition of early atherogenesis in transgenic mice by human apolipoprotein AI.
Epidemiological surveys have identified a strong inverse relationship between the amount in the plasma of high density lipoproteins (HDL), apolipoprotein AI (ApoA-I), the major protein component of HDL, and the risk for atherosclerosis in humans. It is not known if this relationship arises from a direct antiatherogenic effect of these plasma components or if it is the result of other factors also associated with increases in ApoA-I and HDL levels. Because some strains of mice are susceptible to diet-induced formation of preatherosclerotic fatty streak lesions, and because of available techniques for the genetic manipulation of this organism, the murine system offers a unique setting in which to investigate the process of early atherogenesis. To test the hypothesis that induction of a high plasma concentration of ApoA-I and HDL would inhibit this process, we studied the effects of atherogenic diets on transgenic mice expressing high amounts of human ApoA-I. We report that transgenic mice with high plasma ApoA-I and HDL levels were significantly protected from the development of fatty streak lesions.
Rubin
E M
EM
Division of Research Medicine and Radiation Biophysics, Lawrence Berkeley Laboratory, University of California, Berkeley 94720.
Krauss
R M
RM
Spangler
E A
EA
Verstuyft
J G
JG
Clift
S M
SM
D000818:Animals; D001011:Aorta / Q000473:pathology*; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000097:blood / Q000235:genetics*; D001161:Arteriosclerosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002079:Butter; D002791:Cholesterol, Dietary; D004036:Diet, Atherogenic; D020022:Genetic Predisposition to Disease; D006801:Humans; D008075:Lipoproteins, HDL / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000473:pathology
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D002791:Cholesterol, Dietary; D008075:Lipoproteins, HDL; D002079:Butter