LAL (Lysosomal Acid Lipase) Promotes Reverse Cholesterol Transport In Vitro and In Vivo
Autor: | Kristin Bowden, Teddy Chan, Hong Du, Gregory A. Grabowski, Gordon A. Francis, You-Hai Xu, Joshua A. Dubland |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Mice 129 Strain Oxysterol Lipoproteins ABCG8 030204 cardiovascular system & hematology Article Cell Line Feces 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Animals ATP Binding Cassette Transporter Subfamily G Member 5 ATP Binding Cassette Transporter Subfamily G Member 1 Mice Knockout Apolipoprotein A-I biology Chemistry Cholesterol ATP Binding Cassette Transporter Subfamily G Member 8 Reverse cholesterol transport Biological Transport Sterol Esterase Molecular biology 030104 developmental biology Liver ABCG1 ABCA1 Macrophages Peritoneal biology.protein ABCG5 lipids (amino acids peptides and proteins) Cardiology and Cardiovascular Medicine ATP Binding Cassette Transporter 1 Lipoprotein |
Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 38:1191-1201 |
ISSN: | 1524-4636 1079-5642 |
DOI: | 10.1161/atvbaha.117.310507 |
Popis: | Objective— To explore the role of LAL (lysosomal acid lipase) in macrophage cholesterol efflux and whole-body reverse cholesterol transport. Approach and Results— Immortalized peritoneal macrophages from lal −/− mice showed reduced expression of ABCA1 (ATP-binding cassette transporter A1) and ABCG1 (ATP-binding cassette transporter G1), reduced production of the regulatory oxysterol 27-hydroxycholesterol, and impaired suppression of cholesterol synthesis on exposure to acetylated low-density lipoprotein when compared with lal +/+ macrophages. LAL-deficient mice also showed reduced hepatic ABCG5 (ATP-binding cassette transporter G5) and ABCG8 (ATP-binding cassette transporter G8) expression compared with lal +/+ mice. LAL-deficient macrophages loaded with [ 3 H]-cholesteryl oleate-labeled acetylated low-density lipoprotein showed impaired efflux of released [ 3 H]-cholesterol to apoA-I (apolipoprotein A-I), with normalization of [ 3 H]-cholesteryl ester levels and partial correction of ABCA1 expression and cholesterol efflux to apoA-I when treated with exogenous rhLAL (recombinant human LAL protein). LAL-deficient mice injected intraperitoneally with lal −/− macrophages cholesterol loaded and labeled in the same way exhibited only 1.55±0.35% total injected [ 3 H]-cholesterol counts appearing in the feces for 48 h (n=30), compared with 5.38±0.92% in lal +/+ mice injected with labeled lal +/+ macrophages (n=27), P −/− macrophages into lal +/+ mice resulted in a significant increase in reverse cholesterol transport (2.60±0.46% of 3 H-cholesterol counts in feces at 48 hours [n=19]; P −/− mice). Conclusions— These results indicate a critical role for LAL in promoting both macrophage and whole-body reverse cholesterol transport and the ability of supplemental LAL to be taken up and correct reverse cholesterol transport in vivo. |
Databáze: | OpenAIRE |
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