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Titolo:
A direct role for the macrophage low density lipoprotein receptor in atherosclerotic lesion formation
Autore:
Linton, MF; Babaev, VR; Gleaves, LA; Fazio, S;
Indirizzi:
Vanderbilt Univ, Sch Med, Div Endocrinol, Med Ctr,Dept Med, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 ,Dept Med, Nashville, TN 37232 USA Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 pt Pathol, Nashville, TN 37232 USA Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 Pharmacol, Nashville, TN 37232 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 27, volume: 274, anno: 1999,
pagine: 19204 - 19210
SICI:
0021-9258(19990702)274:27<19204:ADRFTM>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHOLESTERYL ESTER ACCUMULATION; MOUSE PERITONEAL-MACROPHAGES; BONE-MARROW TRANSPLANTATION; ISOLATED HUMAN LYMPHOCYTES; FAMILIAL HYPERCHOLESTEROLEMIA; APOLIPOPROTEIN-E; KNOCKOUT MICE; CANINE BETA; LDL; SUSCEPTIBILITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Linton, MF Vanderbilt Univ, Sch Med, Div Endocrinol, Med Ctr,Dept Med, 715Med Res Bldg 2, Nashville, TN 37232 USA Vanderbilt Univ 715 Med Res Bldg 2Nashville TN USA 37232 2 USA
Citazione:
M.F. Linton et al., "A direct role for the macrophage low density lipoprotein receptor in atherosclerotic lesion formation", J BIOL CHEM, 274(27), 1999, pp. 19204-19210

Abstract

To evaluate the contribution of the macrophage low density lipoprotein receptor (LDLR) to atherosclerotic lesion formation, we performed bone marrow transplantation studies in different mouse strains. First, LDLR(-/-) mice were transplanted with either LDLR(+/+) marrow or LDLR(-/-) marrow and were challenged with an atherogenic Western type diet. The diet caused severe hypercholesterolemia of a similar degree in the two groups, and no differences in the aortic lesion area were detected. Thus, macrophage LDLR expressiondoes not influence foam cell lesion formation in the setting of extreme LDL accumulation. To determine whether macrophage LDLR expression affects foam cell formation under conditions of moderate, non-LDL by. perlipidemia, wetransplanted C57BL/6 mice with either LDLR(-/-) marrow (experimental group) or LDLR(+/+) marrow (controls). Cholesterol levels were not significantlydifferent between the two groups at baseline or after 6 weeks on a butterfat diet, but were 40% higher in the experimental mice after 13 weeks, mostly due to accumulation of beta-very low density lipoprotein (beta-VLDL). Despite the increase in cholesterol levels, mice receiving LDLR(-/-) marrow developed 63% smaller lesions than controls, demonstrating that macrophage LDLR affects the rate of foam cell formation when the atherogenic stimulus isbeta-VLDL. We conclude that the macrophage LDLR is responsible for a significant portion of lipid accumulation in foam cells under conditions of dietary stress.

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Documento generato il 04/12/20 alle ore 06:25:56