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Journal of Lipid Research, Vol. 43, 1734-1742, October 2002
Copyright © 2002 by Lipid Research, Inc.

Mechanisms of HDL deficiency in mice overexpressing human apoA-II

Josep Julve^*,, Joan Carles Escolà-Gil^*,, Vicent Ribas^*,, Francesc González-Sastre^*,, Jordi Ordóñez-Llanos^*,, José Luis Sánchez-Quesada^*, and Francisco Blanco-Vaca^1,*,

^* Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain

¹ To whom correspondence should be addressed. e-mail: fblancova{at}hsp.santpau.es

To ascertain the mechanisms underlying the hypoalphalipoproteinemia present in mice overexpressing human apolipoprotein A-II (apoA-II) (line 11.1), radiolabeled HDL or apoA-I were injected into mice. Fractional catabolic rate of [³H]cholesteryl oleoyl ether HDL ([³H]HDL) was 2-fold increased in 11.1 transgenic mice compared with control mice and this was concomitant with increased radioactivity in liver, gonads, and adrenals. However, scavenger receptor class B, type I (SR-BI) was increased only in adrenals. [³H]HDL of 11.1 transgenic mice presented greater binding but decreased uptake compared with control mice when Chinese hamster ovary cells transfected with SR-BI were used, thereby pointing to unknown but SR-BI-independent mechanisms as being responsible for the increased ³H-radioactivity seen in liver and gonads. Synthesis rate (SR) of plasma [³H]HDL was 2-fold decreased in 11.1 transgenic mice. Mouse ¹²⁵I-apoA-I was 2-fold more rapidly catabolized (mainly by the kidney) in transgenic mice. Mouse apoA-I displacement from HDL by the addition of isolated human apoA-II was reproduced ex vivo; thus, this mechanism may be involved in the increased renal catabolism of apoA-I. ApoA-I SR was 2-fold decreased in 11.1 transgenic mice and this was concomitant with a 2.3-fold decrease in hepatic apoA-I mRNA abundance.

Our findings show that multiple mechanisms are involved in the HDL deficiency presented by mice overexpressing human apoA-II.

Abbreviations: apo, apolipoprotein; FCR, fractional catabolic rate; LpA-I, high-density lipoprotein with apoA-I without apoA-II; LpA-I/A-II, high-density lipoprotein with apoA-I and apoA-II; SR, synthesis rate; SR-BI, scavenger receptor class B, type I

Supplementary key words apoA-I • apoA-II transgenic mice • hypoalphalipoproteinemia • lipoprotein metabolism

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