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-I 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 18weeks, 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 18weeks 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 10weeks 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. Copyright (c) 2010 Elsevier Inc. All rights reserved.
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-I 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 18weeks, 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 18weeks 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 10weeks 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. Copyright (c) 2010 Elsevier Inc. All rights reserved.
Authors: James R Bayrer; Sridevi Mukkamala; Elena P Sablin; Paul Webb; Robert J Fletterick Journal: Proc Natl Acad Sci U S A Date: 2015-02-09 Impact factor: 11.205
Authors: Illiana Meurs; Laura Calpe-Berdiel; Kim L L Habets; Ying Zhao; Suzanne J A Korporaal; A Mieke Mommaas; Emmanuelle Josselin; Reeni B Hildebrand; Dan Ye; Ruud Out; Johan Kuiper; Theo J C Van Berkel; Giovanna Chimini; Miranda Van Eck Journal: PLoS One Date: 2012-03-05 Impact factor: 3.240
Authors: Justyna Horodyska; Ruth M Hamill; Henry Reyer; Nares Trakooljul; Peadar G Lawlor; Ursula M McCormack; Klaus Wimmers Journal: Front Genet Date: 2019-02-19 Impact factor: 4.599
Authors: Gina M DeStefano; Mazen Kurban; Kwame Anyane-Yeboa; Claudia Dall'Armi; Gilbert Di Paolo; Heather Feenstra; Nanette Silverberg; Luis Rohena; Larissa D López-Cepeda; Vaidehi Jobanputra; Katherine A Fantauzzo; Maija Kiuru; Marija Tadin-Strapps; Antonio Sobrino; Anna Vitebsky; Dorothy Warburton; Brynn Levy; Julio C Salas-Alanis; Angela M Christiano Journal: PLoS Genet Date: 2014-05-15 Impact factor: 5.917