Atherosclerosis in transgenic mice overexpressing apolipoprotein A-II.
Concentrations of plasma high density lipoprotein (HDL) are inversely correlated with atherosclerotic coronary artery disease. The two most abundant protein constituents of HDL are apolipoproteins A-I and A-II (apoA-I and apoA-II). ApoA-I is required for assembly of HDL and, when overexpressed in transgenic mice, confers resistance to early atherosclerosis. The present studies reveal that transgenic mice that overexpress mouse apoA-II had elevated HDL-cholesterol concentrations but, nevertheless, exhibited increased atherosclerotic lesion development as compared to normal mice. The HDL in the transgenic mice was larger and had an increased ratio of apoA-II to apoA-I. Thus, both the composition and amount of HDL appear to be important determinants of atherosclerosis.
Warden
C H
CH
Department of Medicine, University of California, Los Angeles 90024.
Hedrick
C C
CC
Qiao
J H
JH
Castellani
L W
LW
Lusis
A J
AJ
D000818:Animals; D016632:Apolipoprotein A-I / Q000502:physiology; D016633:Apolipoprotein A-II / Q000235:genetics / Q000502:physiology*; D001161:Arteriosclerosis / Q000097:blood* / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D003433:Crosses, Genetic; D005260:Female; D008075:Lipoproteins, HDL / Q000097:blood / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D008075:Lipoproteins, HDL; D002784:Cholesterol