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, Francisco Blanco-Vaca

Research output: Contribution to journalArticleResearchpeer-review

23 Citations (Scopus)

Abstract

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-radio-activity 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.
Original languageEnglish
Pages (from-to)1734-1742
JournalJournal of Lipid Research
Volume43
DOIs
Publication statusPublished - 1 Oct 2002

Keywords

  • Hypoalphalipoproteinemia
  • Lipoprotein metabolism
  • apoA-I
  • apoA-II transgenic mice

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