Increased prebeta-high density lipoprotein, apolipoprotein AI, and phospholipid in mice expressing the human phospholipid transfer protein and human apolipoprotein AI transgenes.

Jiang, X; Francone, O L; Bruce, C; Milne, R; Mar, J; Walsh, A; Breslow, J L; Tall, A R

Jiang, X; Francone, O L; Bruce, C; Milne, R; Mar, J; Walsh, A; Breslow, J L; Tall, A R.

Afiliación

Jiang X; Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY 10032, USA.

J Clin Invest ; 98(10): 2373-80, 1996 Nov 15.

Article en En | MEDLINE | ID: mdl-8941656

RESUMEN

Human plasma phospholipid transfer protein (PLTP) circulates bound to high density lipoprotein (HDL) and mediates both net transfer and exchange of phospholipids between different lipoproteins. However, its overall function in lipoprotein metabolism is unknown. To assess the effects of increased plasma levels of PLTP, human PLTP transgenic mice were established using the human PLTP gene driven by its natural promoter. One line of PLTP transgenic mice with moderate expression of PLTP mRNA and protein was obtained. The order of human PLTP mRNA expression in tissues was: liver, kidney, brain, small intestine > lung > spleen > heart, adipose tissue. Western blotting using a human PLTP monoclonal antibody revealed authentic human PLTP (Mr 80 kD) in plasma. Plasma PLTP activity was increased by 29% in PLTP transgenic mice. However, plasma lipoprotein analysis, comparing PLTP transgenic mice to control littermates, revealed no significant changes in the plasma lipoprotein lipids or apolipoproteins. Since previous studies have shown that human cholesteryl ester transfer protein and lecithin:cholesterol acyltransferase only function optimally in human apoAI transgenic mice, the human PLTP transgenic mice were cross-bred with human apoAI transgenic mice. In the human apoAI transgenic background, PLTP expression resulted in increased PLTP activity (47%), HDL phospholipid (26%), cholesteryl ester (24%), free cholesterol (37%), and apoAI (22%). There was a major increase of apoAI in prebeta-HDL (56%) and a small increase in alpha-HDL (14%). The size distribution of HDL particles within alpha- and prebeta-migrating species was not changed. The results suggest that PLTP increases the influx of phospholipid and secondarily cholesterol into HDL, leading to an increase in potentially antiatherogenic prebeta-HDL particles.

Asunto(s)

Proteínas Portadoras/genética; Proteínas Portadoras/metabolismo; Regulación de la Expresión Génica; Proteínas de la Membrana/genética; Proteínas de la Membrana/metabolismo; Ratones Transgénicos/genética; Ratones Transgénicos/metabolismo; Proteínas de Transferencia de Fosfolípidos; Animales; Anticuerpos Monoclonales/inmunología; Apolipoproteína A-I/genética; Apolipoproteína A-I/metabolismo; Apolipoproteínas/análisis; Apolipoproteínas/sangre; Western Blotting; Encéfalo/metabolismo; Proteínas Portadoras/sangre; Proteínas Portadoras/inmunología; Colesterol/metabolismo; Ésteres del Colesterol/metabolismo; Clonación Molecular; ADN/análisis; Femenino; Humanos; Intestino Delgado/metabolismo; Riñón/metabolismo; Lipoproteínas/análisis; Lipoproteínas/sangre; Lipoproteínas HDL/metabolismo; Hígado/metabolismo; Pulmón/metabolismo; Proteínas de la Membrana/sangre; Proteínas de la Membrana/inmunología; Ratones; Ratones Endogámicos C57BL; Ratones Endogámicos CBA; Músculos/metabolismo; Miocardio/metabolismo; Hibridación de Ácido Nucleico; ARN/análisis; ARN Mensajero/análisis; ARN Mensajero/metabolismo; Bazo/metabolismo

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ratones Transgénicos / Proteínas Portadoras / Regulación de la Expresión Génica / Proteínas de Transferencia de Fosfolípidos / Proteínas de la Membrana Idioma: En Revista: J Clin Invest Año: 1996 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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