Overexpression of low density lipoprotein receptor eliminates apolipoprotein B100-containing lipoproteins from circulation and markedly prevents early atherogenesis in apolipoprotein E-deficient mice

Toshinori Murayama, Masayuki Yokode, Hisanori Horiuchi, Hiroyuki Yoshida, Hideto Sano, Toru Kita

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Apolipoprotein E (ApoE) plays a pivotal role in the metabolism of apolipoprotein B (apoB)-containing lipoproteins. The defective apoE gene in humans can cause elevated plasma levels of apoB-containing lipoproteins such as chylomicron remnant and intermediate density lipoprotein (IDL). In this study, we examined whether liver-selective high-level expression of low-density lipoprotein receptor (LDLR) could affect the lipoprotein profile and atherogenesis in apoE-deficient (apoE-/-) mice. ApoE knockout mice expressing LDLR transgene in liver [apoE-/-;Tg(LDLR+/-)] were prepared after mating apoE-/- mice with the human LDLR transgenic mice. The apoE-/-;Tg(LDLR+/-) and littermate apoE-/- mice were fed a normal diet and sacrificed at 18 weeks of age. (1) The plasma levels of cholesterol and triglyceride in apoE-/-;Tg(LDLR+/-) mice were 51 and 33% lower than those of apoE-/- mice, respectively. (2) In the plasma of apoE-/-;Tg(LDLR+/-) mice, the levels of apoB-containing lipoprotein were reduced and apoB100-containing particles were totally eliminated. (3) By histochemical analysis, apoE-/-;Tg(LDLR+/-) mice showed drastic suppression of early atherogenesis; the lesion area of these mice was 1/70 of that in the littermate apoE-/- mice. These results indicate that, even in apoE-defective subjects, induction of hepatic LDLR expression could protect from early atherogenesis.

Original languageEnglish
Pages (from-to)295-302
Number of pages8
JournalAtherosclerosis
Volume153
Issue number2
DOIs
Publication statusPublished - 2000
Externally publishedYes

Keywords

  • Apolipoprotein
  • Atherosclerosis
  • Lipoproteins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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