Apolipoprotein B secretion and atherosclerosis are decreased in mice with phospholipid-transfer protein deficiency

XC Jiang, S Qin, C Qiao, K Kawano, M Lin, A Skold… - Nature medicine, 2001 - nature.com
XC Jiang, S Qin, C Qiao, K Kawano, M Lin, A Skold, X Xiao, AR Tall
Nature medicine, 2001nature.com
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 …
Abstract
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.
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