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- Title
Apolipoprotein B secretion and atherosclerosis are decreased in mice with phospholipid-transfer protein deficiency.
- Authors
Jiang, Xian-Cheng; Qin, Shucun; Qiao, Chunping; Kawano, Koichi; Lin, Min; Skold, Anna; Xiao, Xiao; Tall, Alan R.
- 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.
- Subjects
APOLIPOPROTEINS; PHOSPHOLIPIDS; ATHEROSCLEROSIS; LIVER cells
- Publication
Nature Medicine, 2001, Vol 7, Issue 7, p847
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/89977