Advertisement

Research Article Free access | 10.1172/JCI117832

Decreased cholesteryl ester transfer protein (CETP) mRNA and protein and increased high density lipoprotein following lipopolysaccharide administration in human CETP transgenic mice.

L Masucci-Magoulas, P Moulin, X C Jiang, H Richardson, A Walsh, J L Breslow, and A Tall

Department of Medicine, College of Physicians and Surgeons, Columbia University, New York 10032, USA.

Find articles by Masucci-Magoulas, L. in: PubMed | Google Scholar

Department of Medicine, College of Physicians and Surgeons, Columbia University, New York 10032, USA.

Find articles by Moulin, P. in: PubMed | Google Scholar

Department of Medicine, College of Physicians and Surgeons, Columbia University, New York 10032, USA.

Find articles by Jiang, X. in: PubMed | Google Scholar

Department of Medicine, College of Physicians and Surgeons, Columbia University, New York 10032, USA.

Find articles by Richardson, H. in: PubMed | Google Scholar

Department of Medicine, College of Physicians and Surgeons, Columbia University, New York 10032, USA.

Find articles by Walsh, A. in: PubMed | Google Scholar

Department of Medicine, College of Physicians and Surgeons, Columbia University, New York 10032, USA.

Find articles by Breslow, J. in: PubMed | Google Scholar

Department of Medicine, College of Physicians and Surgeons, Columbia University, New York 10032, USA.

Find articles by Tall, A. in: PubMed | Google Scholar

Published April 1, 1995 - More info

Published in Volume 95, Issue 4 on April 1, 1995
J Clin Invest. 1995;95(4):1587–1594. https://doi.org/10.1172/JCI117832.
© 1995 The American Society for Clinical Investigation
Published April 1, 1995 - Version history
View PDF
Abstract

The plasma cholesteryl ester transfer protein (CETP) mediates the exchange of HDL cholesteryl esters (CE) and VLDL triglycerides leading to catabolism of HDL. There is some evidence that HDL ameliorates the toxicity of LPS, and LPS is known to influence several enzymes affecting HDL metabolism. Therefore, the effects of LPS on CETP and plasma lipoproteins were examined in human CETP transgenic mice. Administration of LPS to mice expressing a CETP transgene linked to its natural flanking sequences (NFR-CETP Tg) resulted in a rapid marked decrease in hepatic CETP mRNA and plasma CETP concentration. Corticosteroid injection produced a similar decrease in hepatic CETP mRNA and adrenalectomy abolished this response to LPS. LPS caused disproportionate reductions in plasma CETP activity compared to mass, and was found to be a potent inhibitor of CETP activity when added directly to plasma. LPS was injected into mice expressing (A) a human apoA-I transgene, (B) apoA-I and NFR-CETP transgenes, or (C) apoA-I and LPS-inducible metallothionein promoter-driven CETP transgenes, producing (A) minimal changes in HDL cholesterol, (B) decreased plasma CETP and increased HDL cholesterol, and (C) increased plasma CETP and decreased HDL cholesterol. Thus, LPS administration produces a profound decrease in hepatic CETP mRNA, primarily as a result of adrenal corticosteroid release. The decrease in plasma CETP activity after LPS administration may reflect both this effect as well as a direct interaction between CETP and LPS. The decrease of CETP in response to LPS has major effects on HDL levels, and may represent an adaptive response to preserve or increase HDL and thereby modify the response to LPS.

Images.

Browse pages

Click on an image below to see the page. View PDF of the complete article

Version history
  • Version 1 (April 1, 1995): No description
Advertisement
Advertisement