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Titolo:
Retroviral gene therapy in ApoE-deficient mice - ApoE expression in the artery wall reduces early foam cell lesion formation
Autore:
Hasty, AH; Linton, MF; Brandt, SJ; Babaev, VR; Gleaves, LA; Fazio, S;
Indirizzi:
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 Med, Nashville, TN USA Vanderbilt Univ Nashville TN USA v, Med Ctr, Dept Med, Nashville, TN USA Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 Pharmacol, Nashville, TN 37232 USA Vanderbilt Univ, Med Ctr, Dept Cell Biol, Nashville, TN USA Vanderbilt Univ Nashville TN USA Ctr, Dept Cell Biol, Nashville, TN USA Vanderbilt Univ, Med Ctr, Dept Vet Affairs, Nashville, TN USA Vanderbilt Univ Nashville TN USA tr, Dept Vet Affairs, Nashville, TN USA
Titolo Testata:
CIRCULATION
fascicolo: 19, volume: 99, anno: 1999,
pagine: 2571 - 2576
SICI:
0009-7322(19990518)99:19<2571:RGTIAM>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
BONE-MARROW TRANSPLANTATION; HUMAN APOLIPOPROTEIN-E; LIPOPROTEIN METABOLISM; CDNA CLONE; ATHEROSCLEROSIS; MACROPHAGES; CHOLESTEROL; SECRETION; INHIBITION; PROTEIN;
Keywords:
apolipoproteins; atherosclerosis; genes; cholesterol;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Linton, MF Vanderbilt Univ, Sch Med, Div Endocrinol, 715 Med Res Bldg 2, Nashville, TN Vanderbilt Univ 715 Med Res Bldg 2 Nashville TN USA 37232 e, TN
Citazione:
A.H. Hasty et al., "Retroviral gene therapy in ApoE-deficient mice - ApoE expression in the artery wall reduces early foam cell lesion formation", CIRCULATION, 99(19), 1999, pp. 2571-2576

Abstract

Background-Apolipoprotein E (apoE) has long been known to play an important role in the clearance of plasma lipoproteins, More recently, a direct role for apoE in delaying atherogenesis has been proposed. Macrophage production of apoE in the artery wall has been demonstrated to provide protection against atherosclerotic lesion development independently from its role in lipoprotein clearance. However, whether macrophage apoE can affect lesion growth at all stages of atherogenesis remains to be established. Methods and Results-To evaluate the role of macrophage apoE in different stages of atherogenesis, as well as to establish a novel gene therapy approach to atherosclerotic vascular disease, we used an apoE-expressing retrovirus to transduce apoE-deficient (-/-) bone marrow for transplantation into apoE(-/-) recipient mice. Three weeks after bone marrow transplantation, apoE was expressed from arterial macrophages and was detectable in plasma associated with lipoproteins at 0.5% to 1% of normal levels but did not affect plasma cholesterol levels. We used 2 groups of recipient mice: younger micewith lesions consisting primarily of foam cells and older mice with more advanced lesions. When either the mouse or human apoE transgenes were expressed in mice from 5 to 13 weeks of age, there was a significant reduction inlesion area, whereas no effects were detected in mice that expressed apoE from 10 to 26 weeks of age. Conclusions-We demonstrate that arterial macrophage apoE secretion can delay atherogenesis if expressed during foam cell formation but is not beneficial during the later stages of atherogenesis, These data also provide evidence that apoE transgene expression from arterial macrophages may have therapeutic applications.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 06:51:51