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Effect of macrophage-derived apolipoprotein E on hyperlipidemia and atherosclerosis of LDLR-deficient mice.
Biochem Biophys Res Commun. 2004 Apr 23; 317(1):223-9.BB

Abstract

LDL receptor-deficient (LDLR(-/-)) mice fed a Western diet exhibit severe hyperlipidemia and develop significant atherosclerosis. Apolipoprotein E (apoE) is a multifunctional protein synthesized by hepatocytes and macrophages. We sought to determine effect of macrophage apoE deficiency on severe hyperlipidemia and atherosclerosis. Female LDLR(-/-) mice were lethally irradiated and reconstituted with bone marrow from either apoE(-/-) or apoE(+/+) mice. Four weeks after transplantation, recipient mice were fed a Western diet for 8 weeks. Reconstitution of LDLR(-/-) mice with apoE(-/-) bone marrow resulted in a slight reduction in plasma apoE levels and a dramatic reduction in accumulation of apoE and apoB in the aortic wall. Plasma lipid levels were unaffected when mice had mild hyperlipidemia on a chow diet, whereas IDL/LDL cholesterol levels were significantly reduced when mice developed severe hyperlipidemia on the Western diet. The hepatic VLDL production rate of mice on the Western diet was decreased by 46% as determined by injection of Triton WR1339 to block VLDL clearance. Atherosclerotic lesions in the proximal aorta were significantly reduced, partially due to reduction in plasma total cholesterol levels (r=0.56; P<0.0001). Thus, macrophage apoE-deficiency alleviates severe hyperlipidemia by slowing hepatic VLDL production and consequently reduces atherosclerosis in LDLR(-/-) mice.

Authors+Show Affiliations

Department of Radiology, University of Virginia, Charlottesville 22908, USA. ws4v@virginia.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15047172

Citation

Shi, Weibin, et al. "Effect of Macrophage-derived Apolipoprotein E On Hyperlipidemia and Atherosclerosis of LDLR-deficient Mice." Biochemical and Biophysical Research Communications, vol. 317, no. 1, 2004, pp. 223-9.
Shi W, Wang X, Wong J, et al. Effect of macrophage-derived apolipoprotein E on hyperlipidemia and atherosclerosis of LDLR-deficient mice. Biochem Biophys Res Commun. 2004;317(1):223-9.
Shi, W., Wang, X., Wong, J., Hedrick, C. C., Wong, H., Castellani, L. W., & Lusis, A. J. (2004). Effect of macrophage-derived apolipoprotein E on hyperlipidemia and atherosclerosis of LDLR-deficient mice. Biochemical and Biophysical Research Communications, 317(1), 223-9.
Shi W, et al. Effect of Macrophage-derived Apolipoprotein E On Hyperlipidemia and Atherosclerosis of LDLR-deficient Mice. Biochem Biophys Res Commun. 2004 Apr 23;317(1):223-9. PubMed PMID: 15047172.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of macrophage-derived apolipoprotein E on hyperlipidemia and atherosclerosis of LDLR-deficient mice. AU - Shi,Weibin, AU - Wang,Xuping, AU - Wong,Jack, AU - Hedrick,Catherine C, AU - Wong,Howard, AU - Castellani,Lawrence W, AU - Lusis,Aldons J, PY - 2004/02/19/received PY - 2004/3/30/pubmed PY - 2004/5/12/medline PY - 2004/3/30/entrez SP - 223 EP - 9 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 317 IS - 1 N2 - LDL receptor-deficient (LDLR(-/-)) mice fed a Western diet exhibit severe hyperlipidemia and develop significant atherosclerosis. Apolipoprotein E (apoE) is a multifunctional protein synthesized by hepatocytes and macrophages. We sought to determine effect of macrophage apoE deficiency on severe hyperlipidemia and atherosclerosis. Female LDLR(-/-) mice were lethally irradiated and reconstituted with bone marrow from either apoE(-/-) or apoE(+/+) mice. Four weeks after transplantation, recipient mice were fed a Western diet for 8 weeks. Reconstitution of LDLR(-/-) mice with apoE(-/-) bone marrow resulted in a slight reduction in plasma apoE levels and a dramatic reduction in accumulation of apoE and apoB in the aortic wall. Plasma lipid levels were unaffected when mice had mild hyperlipidemia on a chow diet, whereas IDL/LDL cholesterol levels were significantly reduced when mice developed severe hyperlipidemia on the Western diet. The hepatic VLDL production rate of mice on the Western diet was decreased by 46% as determined by injection of Triton WR1339 to block VLDL clearance. Atherosclerotic lesions in the proximal aorta were significantly reduced, partially due to reduction in plasma total cholesterol levels (r=0.56; P<0.0001). Thus, macrophage apoE-deficiency alleviates severe hyperlipidemia by slowing hepatic VLDL production and consequently reduces atherosclerosis in LDLR(-/-) mice. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/15047172/Effect_of_macrophage_derived_apolipoprotein_E_on_hyperlipidemia_and_atherosclerosis_of_LDLR_deficient_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006291X04005170 DB - PRIME DP - Unbound Medicine ER -