Apolipoprotein B secretion and atherosclerosis are decreased in mice with phospholipid-transfer protein deficiency
Xian-Cheng Jiang1, Shucun Qin1, Chunping Qiao2, Koichi Kawano1, Min Lin1, Anna Skold2, Xiao Xiao2
& Alan R. Tall1
1
Division of Molecular Medicine, Department of Medicine, Columbia University, New York, New York, USA
2
Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Correspondence should be addressed to Alan R. Tall art1@columbia.edu
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.
