Homozygous disruption of Pctp modulates atherosclerosis in apolipoprotein E-deficient mice.
Phosphatidylcholine transfer protein (PC-TP) is a cytosolic phospholipid binding protein and a member of the steroidogenic acute regulatory-related transfer domain superfamily. Its tissue distribution includes liver and macrophages. PC-TP regulates hepatic lipid metabolism, and its absence in cholesterol-loaded macrophages is associated with reduced ATP binding cassette transporter A1-mediated lipid efflux and increased susceptibility to apoptosis induced by unesterified cholesterol. To explore a role for PC-TP in atherosclerosis, we prepared PC-TP-deficient/apolipoprotein E-deficient (Pctp(-/-)/Apoe(-/-)) mice and littermate Apoe(-/-) controls. At 16 weeks, atherosclerosis was increased in chow-fed male, but not female, Pctp(-/-)/Apoe(-/-) mice. This effect was associated with increases in plasma lipid concentrations. By contrast, no differences in atherosclerosis were observed between male or female Pctp(-/-)/Apoe(-/-) mice and Apoe(-/-) controls fed a Western-type diet for 16 weeks. At 24 weeks, atherosclerosis in chow-fed male Pctp(-/-)/Apoe(-/-) mice tended to be reduced in proportion to plasma cholesterol. The attenuation of atherosclerosis in female Pctp(-/-)/Apoe(-/-) mice fed chow or the Western-type diet for 24 weeks was not attributable to changes in plasma cholesterol or triglyceride concentrations. These findings suggest that PC-TP modulates the development of atherosclerosis, in part by regulating plasma lipid concentrations.
Wang
Wen-Jun
WJ
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Baez
Juan M
JM
Maurer
Rie
R
Dansky
Hayes M
HM
Cohen
David E
DE
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics* / Q000502:physiology*; D050197:Atherosclerosis / Q000378:metabolism*; D015153:Blotting, Western; D002784:Cholesterol / Q000737:chemistry; D005260:Female; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D008055:Lipids / Q000737:chemistry; D008074:Lipoproteins / Q000737:chemistry; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D049294:Phospholipid Transfer Proteins / Q000235:genetics*
D001057:Apolipoproteins E; D008055:Lipids; D008074:Lipoproteins; D049294:Phospholipid Transfer Proteins; C030104:lipoprotein cholesterol; D002784:Cholesterol