PMID- 10064727
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20131121
IS  - 0022-2275 (Print)
IS  - 0022-2275 (Linking)
VI  - 40
IP  - 3
DP  - 1999 Mar
TI  - Paradoxical effect on atherosclerosis of hormone-sensitive lipase overexpression 
      in macrophages.
PG  - 397-404
AB  - Foam cells formed from receptor-mediated uptake of lipoprotein cholesterol by
      macrophages in the arterial intima are critical in the initiation, progression,
      and stability of atherosclerotic lesions. Macrophages accumulate cholesterol when
      conditions favor esterification by acyl-CoA:cholesterol acyltransferase (ACAT)
      over cholesteryl-ester hydrolysis by a neutral cholesteryl-ester hydrolase, such 
      as hormone-sensitive lipase (HSL), and subsequent cholesterol efflux mediated by 
      extracellular acceptors. We recently made stable transfectants of a murine
      macrophage cell line, RAW 264.7, that overexpressed a rat HSL cDNA and had a
      5-fold higher rate of cholesteryl-ester hydrolysis than control cells. The
      current study examined the effect of macrophage-specific HSL overexpression on
      susceptibility to diet-induced atherosclerosis in mice. A transgenic line
      overexpressing the rat HSL cDNA regulated with a macrophage-specific scavenger
      receptor promoter-enhancer was established by breeding with C57BL/6J mice.
      Transgenic peritoneal macrophages exhibited macrophage-specific 7-fold
      overexpression of HSL cholesterol esterase activity. Total plasma cholesterol
      levels in transgenic mice fed a chow diet were modestly elevated 16% compared to 
      control littermates. After 14 weeks on a high-fat, high-cholesterol diet, total
      cholesterol increased 3-fold, with no difference between transgenics and
      controls. However, HSL overexpression resulted in thicker aortic fatty lesions
      that were 2.5-times larger in transgenic mice. HSL expression in the aortic
      lesions was shown by immunocytochemistry. Atherosclerosis was more advanced in
      transgenic mice exhibiting raised lesions involving the aortic wall, along with
      lipid accumulation in coronary arteries occurring only in transgenics. Thus,
      increasing cholesteryl-ester hydrolysis, without concomitantly decreasing ACAT
      activity or increasing cholesterol efflux, is not sufficient to protect against
      atherosclerosis. hormone-sensitive lipase overexpression in macrophages.
FAU - Escary, J L
AU  - Escary JL
AD  - Lipid Research Laboratory, West Los Angeles VA Medical Center, Los Angeles, CA
      90073, USA.
FAU - Choy, H A
AU  - Choy HA
FAU - Reue, K
AU  - Reue K
FAU - Wang, X P
AU  - Wang XP
FAU - Castellani, L W
AU  - Castellani LW
FAU - Glass, C K
AU  - Glass CK
FAU - Lusis, A J
AU  - Lusis AJ
FAU - Schotz, M C
AU  - Schotz MC
LA  - eng
GR  - HL14197/HL/NHLBI NIH HHS/United States
GR  - HL28481/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Lipid Res
JT  - Journal of lipid research
JID - 0376606
RN  - 0 (Cholesterol Esters)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Receptors, Lipoprotein)
RN  - 0 (Receptors, Scavenger)
RN  - 0 (Scarb1 protein, mouse)
RN  - 0 (Scavenger Receptors, Class B)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 3.1.1.13 (Sterol Esterase)
SB  - IM
MH  - Animals
MH  - Aorta/pathology
MH  - Arteriosclerosis/*genetics/pathology
MH  - Cell Line
MH  - Cholesterol/blood
MH  - Cholesterol Esters/metabolism
MH  - Diet, Atherogenic
MH  - Enhancer Elements, Genetic/genetics
MH  - Female
MH  - Gene Expression Regulation/genetics
MH  - Macrophages, Peritoneal/*enzymology
MH  - *Membrane Proteins
MH  - Mice
MH  - Mice, Transgenic
MH  - Promoter Regions, Genetic/genetics
MH  - Rats
MH  - Receptors, Immunologic/genetics
MH  - *Receptors, Lipoprotein
MH  - Receptors, Scavenger
MH  - Scavenger Receptors, Class B
MH  - Sterol Esterase/*genetics
MH  - Transfection/genetics
EDAT- 1999/03/05 00:00
MHDA- 1999/03/05 00:01
CRDT- 1999/03/05 00:00
PHST- 1999/03/05 00:00 [pubmed]
PHST- 1999/03/05 00:01 [medline]
PHST- 1999/03/05 00:00 [entrez]
PST - ppublish
SO  - J Lipid Res. 1999 Mar;40(3):397-404.