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Titolo:
Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in low density lipoprotein receptor-deficient mice
Autore:
Babaev, VR; Patel, MB; Semenkovich, CF; Fazio, S; Linton, MF;
Indirizzi:
Vanderbilt Univ, Med Ctr, Sch Med, Dept Med,Div Cardiovasc Med, Nashville,TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 iovasc 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 Washington Univ, St Louis, MO 63110 USA Washington Univ St Louis MO USA 63110 ington Univ, St Louis, MO 63110 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 34, volume: 275, anno: 2000,
pagine: 26293 - 26299
SICI:
0021-9258(20000825)275:34<26293:MLLPFC>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
HEPARAN-SULFATE PROTEOGLYCANS; IV HYPERTRIGLYCERIDEMIC VLDL; SMOOTH-MUSCLE CELLS; OXIDIZED LDL; KNOCKOUT MICE; PPAR-GAMMA; IN-VIVO; METABOLISM; INCREASES; LESIONS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Fazio, S Vanderbilt Univ, Med Ctr, Sch Med, Dept Med,Div Cardiovasc Med, Rm 312,MedRes Bldg 2, Nashville, TN 37232 USA Vanderbilt Univ Rm 312,Med ResBldg 2 Nashville TN USA 37232 USA
Citazione:
V.R. Babaev et al., "Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in low density lipoprotein receptor-deficient mice", J BIOL CHEM, 275(34), 2000, pp. 26293-26299

Abstract

The role of macrophage lipoprotein lipase (LPL) expression in atherosclerotic lesion formation was examined in low density lipoprotein receptor (LDLR-/-) mice using dietary conditions designed to induce either fatty streak lesions or complex atherosclerotic lesions. First, LDLR-/- mice chimeric formacrophage LPL expression were created by transplantation of lethally irradiated female LDLR-/- mice with LPL-/- (n = 12) or LPL+/+ (n = 14) fetal liver cells as a source of hematopoietic cells. To induce fatty streak lesions, these mice were fed a Western diet for 8 weeks, resulting in severe hypercholesterolemia, There were no differences in plasma postheparin LPL activity, serum lipid levels, or lipoprotein distribution between these two groups. The mean lesion area in the proximal aorta in LPL-/- --> LDLR-/- mice was significantly reduced by 33% compared with LPL+/+ --> LDLR-/- mice, and a similar reduction (38%) in lesion area was found by en face analysis of the aortae. To induce complex atherosclerotic lesions, female LDLR-/- mice were lethally irradiated, transplanted with LPL-/-(n = 14), LPL+/- (n = 13),or LPL+/+ (n = 14) fetal liver cells, and fed the Western diet for 19 weeks. Serum cholesterol and triglyceride levels did not differ between the three groups. After 19 weeks of diet, the lesions in the proximal aorta were complex with relatively few macrophages expressing LPL protein and mRNA in LPL+/+ --> LDLR-/- mice. Analysis of cross-sections of the proximal aorta demonstrated no differences in the extent of lesion area between the groups, whereas en face analysis of the aortae revealed a dose-dependent effect of macrophage LPL on mean aortic lesion area in LPL-/- --> LDLR-/-, LPL-/+ -->LDLR-/-, and LPL+/+ --> LDLR-/- mice (1.8 +/- 0,2%, 3.5 +/- 0.5% and 5.9 +/- 0,8%, respectively). Taken together, these data indicate that macrophageLPL expression in the artery wall promotes atherogenesis during foam cell lesion formation, but this impact may be limited to macrophage-rich lesions.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 15:36:04