Worsening of diet-induced atherosclerosis in a new model of transgenic rabbit expressing the human plasma phospholipid transfer protein
2011
Masson, David, D. | Deckert, Valérie, V. | Gautier, Thomas, T. | Klein, Alexis, A. | Desrumaux, Catherine | Viglietta, Celine, C. | Pais de Barros, Jean-Paul | Le Guern, Naïg | Grober, Jacques | Labbé, Jérôme, J. | Ménétrier, Franck, F. | Ripoll, Pierre-Jean, P.-J. | Leroux-Coyau, Mathieu, M. | Jolivet, Geneviève | Houdebine, Louis, L. | Lagrost, Laurent, L. | Lipides - Nutrition - Cancer (U866) (LNC) ; Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA) | Services généraux de centre ; Institut National de la Recherche Agronomique (INRA) | Biologie du développement et reproduction (BDR) ; École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS) | Université de Bourgogne, Centre Hospitalier Universitaire de Dijon, Conseil Régional de Bourgogne, Institut National de la Santé et de la Recherche Médicale, Agence Nationale de la Recherche (Atherolip Project), Fondation de France
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. 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. 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.
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