PMID- 29599133
OWN - NLM
STAT- MEDLINE
DCOM- 20190708
LR  - 20190708
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Print)
IS  - 1079-5642 (Linking)
VI  - 38
IP  - 5
DP  - 2018 May
TI  - LAL (Lysosomal Acid Lipase) Promotes Reverse Cholesterol Transport In Vitro and 
      In Vivo.
PG  - 1191-1201
LID - 10.1161/ATVBAHA.117.310507 [doi]
AB  - 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<0.001. To mimic the 
      therapeutic condition of delivery of supplemental LAL in vivo, injection of 
      labeled lal(-/-) 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<0.001 when compared with injection into lal(-/-) 
      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.
CI  - (c) 2018 American Heart Association, Inc.
FAU - Bowden, Kristin L
AU  - Bowden KL
AD  - From the Department of Medicine, Centre for Heart Lung Innovation, Institute for 
      Heart + Lung Health, Providence Health Care Research Institute at St. Paul's 
      Hospital, University of British Columbia, Vancouver, Canada (K.L.B., J.A.D., 
      T.C., G.A.F.).
FAU - Dubland, Joshua A
AU  - Dubland JA
AD  - From the Department of Medicine, Centre for Heart Lung Innovation, Institute for 
      Heart + Lung Health, Providence Health Care Research Institute at St. Paul's 
      Hospital, University of British Columbia, Vancouver, Canada (K.L.B., J.A.D., 
      T.C., G.A.F.).
FAU - Chan, Teddy
AU  - Chan T
AD  - From the Department of Medicine, Centre for Heart Lung Innovation, Institute for 
      Heart + Lung Health, Providence Health Care Research Institute at St. Paul's 
      Hospital, University of British Columbia, Vancouver, Canada (K.L.B., J.A.D., 
      T.C., G.A.F.).
FAU - Xu, You-Hai
AU  - Xu YH
AD  - Division of Human Genetics, Cincinnati Children's Hospital Medical Center, OH 
      (Y.-H.X., G.A.G.).
AD  - Division of Human Genetics, Cincinnati Children's Hospital Medical Center, OH 
      (Y.-H.X., G.A.G.).
FAU - Grabowski, Gregory A
AU  - Grabowski GA
AD  - From the Department of Medicine, Centre for Heart Lung Innovation, Institute for 
      Heart + Lung Health, Providence Health Care Research Institute at St. Paul's 
      Hospital, University of British Columbia, Vancouver, Canada (K.L.B., J.A.D., 
      T.C., G.A.F.).
AD  - Division of Human Genetics, Cincinnati Children's Hospital Medical Center, OH 
      (Y.-H.X., G.A.G.).
AD  - Department of Pediatrics, University of Cincinnati College of Medicine, OH 
      (Y.-H.X., G.A.G.).
FAU - Du, Hong
AU  - Du H
AD  - Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis 
      (H.D.).
FAU - Francis, Gordon A
AU  - Francis GA
AD  - From the Department of Medicine, Centre for Heart Lung Innovation, Institute for 
      Heart + Lung Health, Providence Health Care Research Institute at St. Paul's 
      Hospital, University of British Columbia, Vancouver, Canada (K.L.B., J.A.D., 
      T.C., G.A.F.) gordon.francis@hli.ubc.ca.
LA  - eng
GR  - R01 HL087001/HL/NHLBI NIH HHS/United States
GR  - MOP 79532/CIHR/Canada
GR  - PJT 148883/CIHR/Canada
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180329
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (ABCA1 protein, mouse)
RN  - 0 (ABCG1 protein, mouse)
RN  - 0 (ABCG5 protein, mouse)
RN  - 0 (ABCG8 protein, mouse)
RN  - 0 (APOA1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter 1)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 5)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 8)
RN  - 0 (Apolipoprotein A-I)
RN  - 0 (Lipoproteins)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 3.1.1.13 (LIPA protein, human)
RN  - EC 3.1.1.13 (Sterol Esterase)
RN  - EC 3.1.1.13 (lysosomal acid lipase, mouse)
SB  - IM
MH  - ATP Binding Cassette Transporter 1/genetics/metabolism
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1/genetics/metabolism
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 5/genetics/metabolism
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 8/genetics/metabolism
MH  - Animals
MH  - Apolipoprotein A-I/metabolism
MH  - Biological Transport
MH  - Cell Line
MH  - Cholesterol/blood/*metabolism
MH  - Feces/chemistry
MH  - Lipoproteins/genetics/metabolism
MH  - Liver/metabolism
MH  - Macrophages, Peritoneal/*enzymology
MH  - Mice, 129 Strain
MH  - Mice, Knockout
MH  - Sterol Esterase/deficiency/genetics/*metabolism
PMC - PMC5920716
MID - NIHMS952914
OTO - NOTNLM
OT  - animals
OT  - cholesterol
OT  - macrophages
OT  - mice
OT  - sterol esterase
EDAT- 2018/03/31 06:00
MHDA- 2019/07/10 06:00
PMCR- 2019/05/01
CRDT- 2018/03/31 06:00
PHST- 2015/02/17 00:00 [received]
PHST- 2018/03/13 00:00 [accepted]
PHST- 2018/03/31 06:00 [pubmed]
PHST- 2019/07/10 06:00 [medline]
PHST- 2018/03/31 06:00 [entrez]
PHST- 2019/05/01 00:00 [pmc-release]
AID - ATVBAHA.117.310507 [pii]
AID - 10.1161/ATVBAHA.117.310507 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2018 May;38(5):1191-1201. doi: 
      10.1161/ATVBAHA.117.310507. Epub 2018 Mar 29.