Apolipoprotein B secretion and atherosclerosis are decreased in mice with phospholipid-transfer protein deficiency.
Increased secretion and levels of ApoB-containing lipoproteins (BLp) commonly occur in familial hyperlipidemia, obesity and diabetes. The plasma phospholipid-transfer protein (PLTP) is known to mediate transfer of phospholipids between BLp and HDL during their intravascular metabolism. To address a possible role of PLTP in dyslipidemia and atherogenesis, we bred mice deficient in the gene encoding PLTP (PLTP-deficient mice) using different hyperlipidemic mouse strains. In ApoB-transgenic and ApoE-deficient backgrounds, PLTP deficiency resulted in reduced production and levels of BLp and markedly decreased atherosclerosis. BLp secretion was diminished in hepatocytes from ApoB-transgenic PLTP-deficient mice, a defect that was corrected when PLTP was reintroduced in adenovirus. The studies reveal a major, unexpected role of PLTP in regulating the secretion of BLp and identify PLTP as a therapeutic target.
Jiang
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XC
Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY, USA.
Qin
S
S
Qiao
C
C
Kawano
K
K
Lin
M
M
Skold
A
A
Xiao
X
X
Tall
A R
AR
D000818:Animals; D001055:Apolipoproteins B / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D001161:Arteriosclerosis / Q000150:complications*; D002478:Cells, Cultured; D022781:Hepatocytes / Q000378:metabolism; D008052:Lipid Metabolism, Inborn Errors / Q000150:complications / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
D001055:Apolipoproteins B