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

Nature Medicine volume 7, pages 847–852 (2001)Cite this article

An Erratum to this article was published on 01 August 2001

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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Figure 1: Plasma lipoprotein analysis by FPLC. Pooled mouse plasma (200 μl) was used for FPLC.
Figure 2: SDS–PAGE of ApoB from plasma lipoproteins isolated by ultracentrifuge (d < 1.063 g/ml).
Figure 3: Clearance and production of ApoB in mice.
Figure 4: Pulse-chase analysis of ApoB synthesis and secretion in primary cultures of mouse hepatocytes.
Figure 5: ApoB secretion after adenovirus-mediated overexpression of human PLTP.
Figure 6: Effect of AAV-mediated PLTP expression in PLTP-deficient mice ('0' after protein indicates deficiency).
Figure 7: Quantification of atherosclerosis in the proximal aorta ('0' after protein indicates deficiency).

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Acknowledgements

This study was supported by NIH grant HL54591.

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Authors and Affiliations

  1. Division of Molecular Medicine, Department of Medicine, Columbia University, New York, New York, USA

    Xian-Cheng Jiang, Shucun Qin, Koichi Kawano, Min Lin & Alan R. Tall

  2. Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Chunping Qiao, Anna Skold & Xiao Xiao

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Correspondence to Alan R. Tall.

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Jiang, XC., Qin, S., Qiao, C. et al. Apolipoprotein B secretion and atherosclerosis are decreased in mice with phospholipid-transfer protein deficiency. Nat Med 7, 847–852 (2001). https://doi.org/10.1038/89977

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