Human apolipoprotein A-I prevents atherosclerosis associated with apolipoprotein[a] in transgenic mice.
Elevated levels of apolipoprotein[a] (apo[a]) and apolipoprotein A-I (apoA-I) are associated, respectively, with increased and decreased atherosclerosis risk, in both humans and transgenic mice. To investigate the interactions of these two important lipid-associated proteins, we assessed the effect of expression of human apoA-I and apo[a] transgenes, both singularly and together, on murine atherogenesis. Mice expressing the apo[a] transgene have a lipoprotein profile similar to nontransgenic controls, yet have significantly increased susceptibility to diet-induced atherosclerosis. Compared to mice expressing only the apo[a] transgene, mice expressing both apo[a] and apoA-I transgenes have twofold greater high density lipoprotein (HDL) concentrations and approximately a 20-fold decrease in development of early atherosclerotic lesions. The finding of decreased atherosclerosis in the setting of elevated apo[a] and apoA-I suggests that elevations of apoA-I and HDL have a dominant effect in reducing atherosclerosis susceptibility in various settings, including those not associated with alterations of plasma lipids.
Liu
A C
AC
Human Genome Center, Lawrence Berkeley Laboratory, University of California, Berkeley 94720.
Lawn
R M
RM
Verstuyft
J G
JG
Rubin
E M
EM
D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics* / Q000502:physiology; D001053:Apolipoproteins / Q000235:genetics* / Q000502:physiology; D053241:Apoprotein(a); D001161:Arteriosclerosis / Q000209:etiology / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D004032:Diet; D015870:Gene Expression; D006801:Humans; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D008076:Cholesterol, HDL; D017270:Lipoprotein(a); D008074:Lipoproteins; D002784:Cholesterol; D053241:Apoprotein(a)