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Titolo:
Isoform-specific effects of apolipoprotein E on atherogenesis - Gene transduction studies in mice
Autore:
Yoshida, H; Hasty, AH; Major, AS; Ishiguro, H; Su, YR; Gleaves, LA; Babaev, VR; Linton, MF; Fazio, S;
Indirizzi:
Vanderbilt Univ, Sch Med, Div Cardiovasc Med, Dept Med, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 Dept Med, Nashville, TN 37232 USA Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 pt Pathol, Nashville, TN 37232 USA Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 Pharmacol, Nashville, TN 37232 USA
Titolo Testata:
CIRCULATION
fascicolo: 23, volume: 104, anno: 2001,
pagine: 2820 - 2825
SICI:
0009-7322(200112)104:23<2820:IEOAEO>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
APOE-DEFICIENT MICE; BONE-MARROW TRANSPLANTATION; LDL RECEPTOR-DEFICIENT; III HYPERLIPOPROTEINEMIA; ATHEROSCLEROSIS; EXPRESSION; MACROPHAGES; MECHANISMS; SECRETION; MODULATE;
Keywords:
apolipoproteins; receptors; lipoproteins; proteoglycans;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
23
Recensione:
Indirizzi per estratti:
Indirizzo: Hasty, AH Vanderbilt Univ, Sch Med, Div Cardiovasc Med, Dept Med, 383 Preston Res Bldg, Nashville, TN 37232 USA Vanderbilt Univ 383 Preston Res Bldg Nashville TN USA 37232 USA
Citazione:
H. Yoshida et al., "Isoform-specific effects of apolipoprotein E on atherogenesis - Gene transduction studies in mice", CIRCULATION, 104(23), 2001, pp. 2820-2825

Abstract

Background-We recently used a bone marrow-based gene therapy approach to show that small amounts of retrovirus-derived human apolipoprotein E3 (apoE3) produced by macrophages are protective against early atherosclerosis in apoE-deficient mice. Methods and Results-In the present study, we evaluated whether the effect produced by macrophage-derived apoE3 is related to its ability to bind cellular membranes. To this end, we used apoE2 and apoEcys142, dysfunctional human variants with reduced binding to the LDL receptor or to heparan sulfateproteoglycans, respectively. ApoE-deficient mice, 5 weeks of age, receivedtransplants of apoE(-/-) bone marrow cells transduced with either parentalretrovirus or apoE3, apoE2, or apoEcys142 retroviral vectors. Human apoE was detected by ELISA in the serum of apoE3, apoE2, and apoEcys142 mice as early as 4 weeks after bone marrow transplantation, and at 8 weeks, plasma apoE levels were 55.5 +/- 20.3, 50.5 +/-8.7, and 15.3 +/-7.3 mug/dL, respectively. In all groups, cholesterol levels increased with age but were not affected by apoE expression. As previously demonstrated, the lesion area in male apoE3 mice (3808 +/- 2224 mum(2)/section) was 40% smaller than that in control mice (6503 +/- 3475 mum(2)/section). In apoE2 mice, however, the lesion area was similar to that of controls (5991 +/- 2771 mum(2)/section), and apoEcys142 mice showed an unexpected and significant increase in lesion size (10 320 +/- 6128 mum(2)/section). Thus, transplantation with marrow transfected with receptor binding-defective apoE variants did not replicate the antiatherogenic effect of apoE3. Conclusions-These data provide in vivo evidence suggesting that macrophage-derived apoE delays development of atherosclerosis through a receptor-dependent pathway.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 06:40:49