High plasma HDL concentrations associated with enhanced atherosclerosis in transgenic mice overexpressing lecithin-cholesteryl acyltransferase.
A subset of patients with high plasma HDL concentrations have enhanced rather than reduced atherosclerosis. We have developed a new transgenic mouse model overexpressing human lecithin-cholesteryl acyltransferase (LCAT) that has elevated HDL and increased diet-induced atherosclerosis. LCAT transgenic mouse HDLs are abnormal in both composition and function. Liver uptake of [3H]cholesteryl ether incorporated in transgenic mouse HDL was reduced by 41% compared with control HDL, indicating ineffective transport of HDL-cholesterol to the liver and impaired reverse cholesterol transport. Analysis of this LCAT-transgenic mouse model provides in vivo evidence for dysfunctional HDL as a potential mechanism leading to increased atherosclerosis in the presence of high plasma HDL levels.
Bérard
A M
AM
Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1666, USA.
Föger
B
B
Remaley
A
A
Shamburek
R
R
Vaisman
B L
BL
Talley
G
G
Paigen
B
B
Hoyt
R F
RF
Marcovina
S
S
Brewer
H B
HB
Santamarina-Fojo
S
S
D000818:Animals; D001011:Aorta / Q000473:pathology; D001161:Arteriosclerosis / Q000097:blood* / Q000201:enzymology / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood* / Q000737:chemistry / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
D008055:Lipids; D008075:Lipoproteins, HDL; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase