Worsening of diet-induced atherosclerosis in a new model of transgenic rabbit expressing the human plasma phospholipid transfer protein.

Abstract

OBJECTIVE:

Plasma phospholipid transfer protein (PLTP) is involved in intravascular lipoprotein metabolism. PLTP is known to act through 2 main mechanisms: by remodeling high-density lipoproteins (HDL) and by increasing apolipoprotein (apo) B-containing lipoproteins. The aim of this study was to generate a new model of human PLTP transgenic (HuPLTPTg) rabbit and to determine whether PLTP expression modulates atherosclerosis in this species that, unlike humans and mice, displays naturally very low PLTP activity.

METHODS AND RESULTS:

In HuPLTPTg rabbits, the human PLTP cDNA was placed under the control of the human eF1-α gene promoter, resulting in a widespread tissue expression pattern and in increased plasma PLTP. The HuPLTPTg rabbits showed a significant increase in the cholesterol content of the plasma apoB-containing lipoprotein fractions, with a more severe trait when animals were fed a cholesterol-rich diet. In contrast, HDL cholesterol level was not modified in HuPLTPTg rabbits. Formation of aortic fatty streaks was increased in hypercholesterolemic HuPLTPTg animals as compared with nontransgenic littermates.

CONCLUSIONS:

Human PLTP expression in HuPLTPTg rabbit worsens atherosclerosis as a result of increased levels of atherogenic apoB-containing lipoproteins but not of alterations in their antioxidative protection or in cholesterol content of plasma HDL.

• Authors: David Masson, Valérie Deckert, Thomas Gautier, Alexis Klein, Catherine Desrumaux, Céline Viglietta, Jean-Paul Pais de Barros, Naig Le Guern, Jacques Grober, Jérôme Labbé, Franck Ménétrier, Pierre-Jean Ripoll, Mathieu Leroux-Coyau, Geneviève Jolivet, Louis-Marie Houdebine, Laurent Lagrost
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 31 Issue 4 Pg. 766-74 (Apr 2011) ISSN: 1524-4636 [Electronic] United States
• PMID: 21252068 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins B
• Biomarkers
• Cholesterol, Dietary
• Cholesterol, HDL
• PLTP protein, human
• Peptide Elongation Factor 1
• Phospholipid Transfer Proteins
• Recombinant Proteins

Topics

• Animals
• Animals, Genetically Modified
• Aortic Diseases (etiology, genetics, metabolism, pathology)
• Apolipoproteins B (blood)
• Atherosclerosis (etiology, genetics, metabolism, pathology)
• Biomarkers (blood)
• Cholesterol, Dietary (blood)
• Cholesterol, HDL (blood)
• Disease Models, Animal
• HCT116 Cells
• Humans
• Hypercholesterolemia (complications, metabolism)
• Peptide Elongation Factor 1 (genetics)
• Phospholipid Transfer Proteins (blood, genetics, metabolism)
• Promoter Regions, Genetic
• Rabbits
• Recombinant Proteins (metabolism)
• Time Factors
• Transfection