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Titre du document / Document title

Macrophage ABCA5 deficiency influences cellular cholesterol efflux and increases susceptibility to atherosclerosis in female LDLr knockout mice

Auteur(s) / Author(s)

DAN YE ; MEURS Illiana ; OHIGASHI Megumi ; CALPE-BERDIEL Laura ; HABETS Kim L. L. ; YING ZHAO ; KUBO Yoshiyuki ; YAMAGUCHI Akihito ; VAN BERKEL Theo J. C. ; NISHI Tsuyoshi ; VAN ECK Miranda ;

Résumé / Abstract

Objectives: To determine the role of macrophage ATP-binding cassette transporter A5 (ABCA5) in cellular cholesterol homeostasis and atherosclerotic lesion development. Methods and results: Chimeras with dysfunctional macrophage ABCA5 (ABCA5―M/―M) were generated by transplantation of bone marrow from ABCA5 knockout (ABCA5―/―) mice into irradiated LDLr―/― mice. In vitro, bone marrow-derived macrophages from ABCA5―M/―M chimeras exhibited a 29% (P < 0.001) decrease in cholesterol efflux to HDL, whereas a 21% (P=0.07) increase in cholesterol efflux to apoA-1 was observed. Interestingly, expression of ABCA1, but not ABCG1, was up-regulated in absence of functional ABCA5 in macrophages. To induce atherosclerosis, the transplanted LDLr―/― mice were fed a high-cholesterol Western-type diet (WTD) for 6, 10, or 18 weeks, allowing analysis of effects on initial as well as advanced lesion development. Atherosclerosis development was not affected in male ABCA5―M/―M chimeras after 6, 10, and 18 weeks WTD feeding. However, female ABCA5―M/―M chimeras did develop significantly (P < 0.05) larger aortic root lesions as compared with female controls after 6 and 10 weeks WTD feeding. Conclusions: ABCA5 influences macrophage cholesterol efflux, and selective disruption of ABCA5 in macrophages leads to increased atherosclerotic lesion development in female LDLr―/― mice.

Revue / Journal Title

Biochemical and biophysical research communications    ISSN  0006-291X   CODEN BBRCA9 

Source / Source

2010, vol. 395, no3, pp. 387-394 [8 page(s) (article)]

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Amsterdam, PAYS-BAS  (1959) (Revue)

Mots-clés d'auteur / Author Keywords

Atherosclerosis

;

Macrophage

;

ABCA5

;

Transplantation

;

Cholesterol

;

Localisation / Location

INIST-CNRS, Cote INIST : 8252, 35400018114133.0190

Nº notice refdoc (ud4) : 22765429



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