Protein composition determines the anti-atherogenic properties of HDL in transgenic mice.
High-density lipoprotein (HDL) contains two major proteins, apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II), comprising about 70% and 20% of the total HDL protein mass, respectively. HDL exists in human plasma in two main forms, one containing apoA-I with apoA-II (AI/AII-HDL) and another containing apoA-I without apoA-II (AI-HDL). A strong inverse relationship exists between total plasma HDL concentration and atherosclerosis, but the results of studies examining the relationship between AI-HDL and AI/AII-HDL and atherosclerosis have been conflicting. To determine whether these two HDL populations have different effects on atherogenesis, human apoA-I (AI) and human apoA-I and apoA-II (AI/AII) transgenic mice were produced in an atherosclerosis-susceptible strain. Following an atherogenic diet, despite similar total cholesterol and HDL cholesterol concentrations, the area of atherogenic lesions in the AI/AII mice was 15-fold greater than in the AI animals. These studies show that the protein composition of HDL significantly affects its role in atherogenesis and that AI-HDL is more antiatherogenic than AI/AII-HDL.
Schultz
J R
JR
Life Sciences Division, Lawrence Berkeley Laboratory, University of California, Berkeley 94720.
Verstuyft
J G
JG
Gong
E L
EL
Nichols
A V
AV
Rubin
E M
EM
D000818:Animals; D016632:Apolipoprotein A-I / Q000502:physiology*; D016633:Apolipoprotein A-II / Q000502:physiology*; D001161:Arteriosclerosis / Q000209:etiology*; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D008075:Lipoproteins, HDL