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Titolo:
TRANSGENIC MICE EXPRESSING HIGH-LEVELS OF HUMAN APOLIPOPROTEIN-B DEVELOP SEVERE ATHEROSCLEROTIC LESIONS IN RESPONSE TO A HIGH-FAT DIET
Autore:
PURCELLHUYNH DA; FARESE RV; JOHNSON DF; FLYNN LM; PIEROTTI V; NEWLAND DL; LINTON MF; SANAN DA; YOUNG SG;
Indirizzi:
GLADSTONE INST CARDIOVASC DIS,POB 419100 SAN FRANCISCO CA 94141 GLADSTONE INST CARDIOVASC DIS SAN FRANCISCO CA 94141 UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST SAN FRANCISCO CA 94143 UNIV CALIF SAN FRANCISCO,DEPT MED SAN FRANCISCO CA 94143
Titolo Testata:
The Journal of clinical investigation
fascicolo: 5, volume: 95, anno: 1995,
pagine: 2246 - 2257
SICI:
0021-9738(1995)95:5<2246:TMEHOH>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
CORONARY-ARTERY ATHEROSCLEROSIS; DENSITY LIPOPROTEIN LEVELS; AFRICAN-GREEN MONKEYS; ATHEROGENIC DIET; MESSENGER-RNA; GENE; HYPERCHOLESTEROLEMIA; SUSCEPTIBILITY; MOUSE; CONSUMPTION;
Keywords:
TRANSGENIC MICE; ATHEROSCLEROSIS; APOLIPOPROTEIN B; CHOLESTEROL; LOW DENSITY LIPOPROTEINS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
40
Recensione:
Indirizzi per estratti:
Citazione:
D.A. Purcellhuynh et al., "TRANSGENIC MICE EXPRESSING HIGH-LEVELS OF HUMAN APOLIPOPROTEIN-B DEVELOP SEVERE ATHEROSCLEROTIC LESIONS IN RESPONSE TO A HIGH-FAT DIET", The Journal of clinical investigation, 95(5), 1995, pp. 2246-2257

Abstract

We previously generated transgenic mice expressing human apolipoprotein (apo-) B and demonstrated that the plasma of chow-fed transgenic animals contained markedly increased amounts of LDL (Linton, M. F., R, V, Farese, Jr., G. Chiesa, D. S. Grass, P. Chin, R. E. Hammer, H. H. Hobbs, and S. G. Young 1992. J. Clin. Invest. 92:3029-3037). In this study, we fed groups of transgenic and nontransgenic mice either a chow diet or a diet high in fat (16%) and cholesterol (1.25%). Lipid and lipoprotein levels were assessed, and after 18 wk of diet, the extent of aortic atherosclerotic lesions in each group of animals was quantified, Compared with the female transgenic mice on the chow diet, female transgenic mice on the high-fat diet had higher plasma levels of cholesterol (312+/-17 vs 144+/-7 mg/dl; P < 0.0001) and human apo-B (120+/-8 vs 84+/-3 mg/dl; P < 0.0001), The higher human apo-B levels were due to increased plasma levels of human apo-B48; the human apo-B100 levels did not differ in animals on the two diets, In mice on the high-fat diet, most of the human apo-B48 and apo-B100 was found in LDL-sized particles. Compared with nontransgenic mice on the high-fat diet, the transgenic animals on the high-fat diet had significantly increased levelsof total cholesterol (312+/-17 vs 230+/-19 mg/dl; P < 0.0001) and non-HDL cholesterol (283+/-17 vs 193+/-19 mg/dl; P < 0.0001). The extent of atherosclerotic lesion development within the ascending aorta was quantified by measuring total lesion area in 60 progressive sections, using computer-assisted image analysis. Neither the chow-fed transgenicmice nor the chow-fed nontransgenic mice had significant atherosclerotic lesions. Nontransgenic animals on the high-fat diet had relativelysmall atherosclerotic lesions (< 15,000 mu m(2)/section), almost all of which were confined to the proximal 400 mu m of the aorta near the aortic valve. In contrast, transgenic animals on the high-fat diet hadextensive atherosclerotic lesions (> 160,000 mu m(2)/section) that were widely distributed throughout the proximal 1,200 mu m of the aorta. Thus, human apo-B expression, in the setting of a diet rich in fats, causes severe atherosclerosis in mice.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 16:11:47