Amelioration of Hypertriglyceridemia with Hypo-Alpha-Cholesterolemia in LPL Deficient Mice by Hematopoietic Cell-Derived LPL 英文参考文献.docVIP
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Amelioration of Hypertriglyceridemia with Hypo-Alpha-Cholesterolemia in LPL Deficient Mice by Hematopoietic Cell-Derived LPL 英文参考文献
AmeliorationofHypertriglyceridemiawithHypo-Alpha-
CholesterolemiainLPLDeficientMicebyHematopoietic
Cell-DerivedLPL
YinyuanDing1,LingZhang1,YuhuiWang1,WeiHuang1,YinTang1,LuBai1,ColinJ.D.Ross2,MichaelR.
Hayden2,GeorgeLiu1*
1Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Peking University, Beijing, China, 2Department of Medical Genetics,
CentreforMolecularMedicineandTherapeutics,UniversityofBritishColumbia,Vancouver,BritishColumbia,Canada
Abstract
Background: Macrophage-derived lipoprotein lipase (LPL) has been shown uniformly to promote atherosclerotic lesion
formation while the extent to which it affects plasma lipid and lipoprotein levels varies in wild-type and
hypercholesterolemic mice. It is known that high levels of LPL in the bulk of adipose tissue and skeletal muscle would
certainlymaskthecontributionofmacrophageLPLtometabolismofplasmalipoprotein.Therefore,wechoseLPLdeficient
(LPL-/-) mice with severe hypertriglyceridemia as an alternative model to assess the role of macrophage LPL in plasma
lipoprotein metabolism via bone marrow transplant, through which LPL will be produced mainly by hematopoietic cell-
derivedmacrophages.
-/-
MethodsandResults:HypertriglyceridemicLPL micewerelethallyirradiated,thentransplantedwithbonemarrowfrom
wild-type (LPL ) or LPL-/- mice, respectively. Sixteen weeks later, LPL+/+ RLPL-/- mice displayed significant reduction in
plasma levels of triglyceride and cholesterol (408644.9 vs. 2.760.56103 and 82.967.1 vs. 229.1630.6mg/dl, p,0.05,
respectively), while a2.7-fold increase in plasma high density lipoprotein-cholesterol (p,0.01) was observed, compared
withLPL-/-RLPL-/-controlmice.TheclearanceratefortheoralfatloadtestinLPL+/+RLPL-/-micewasfasterthanthatin
+/+
+/+
LPL-/-RLPL-/- mice, but slower than that in wild-type mice. Liver triglyceride content in LPL RLPL-/- mice was also
significantlyincreased,comparedwithLPL-/-RLPL-/-mice(6.860.7vs.4.660.5mg/gwettissue,p,0.05,n=6).Howev
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