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Titolo:
Transgenic mouse models to study the role of the macrophage scavenger receptor class A in atherosclerosis
Autore:
de Winther, MPJ; Gijbels, MJJ; Van Dijk, KW; Havekes, LM; Hofker, MH;
Indirizzi:
Leiden Univ, Med Ctr, Sylvius Labs, Dept Human & Clin Genet, NL-2300 RA Leiden, Netherlands Leiden Univ Leiden Netherlands NL-2300 RA NL-2300 RA Leiden, Netherlands Leiden Univ, Med Ctr, TNO, PG Gaubius Lab, NL-2300 RA Leiden, Netherlands Leiden Univ Leiden Netherlands NL-2300 RA NL-2300 RA Leiden, Netherlands Leiden Univ, Med Ctr, Dept Internal Med, NL-2300 RA Leiden, Netherlands Leiden Univ Leiden Netherlands NL-2300 RA NL-2300 RA Leiden, Netherlands
Titolo Testata:
INTERNATIONAL JOURNAL OF TISSUE REACTIONS-EXPERIMENTAL AND CLINICAL ASPECTS
fascicolo: 2-3, volume: 22, anno: 2000,
pagine: 85 - 91
SICI:
0250-0868(2000)22:2-3<85:TMMTST>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
LOW-DENSITY-LIPOPROTEIN; A TYPE I/II; GLYCATION END-PRODUCTS; LIPID-PROTEIN ADDUCTS; APOPTOTIC THYMOCYTES; MESSENGER-RNA; MICE; LESIONS; EXPRESSION; RABBITS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: de Winther, MPJ Leiden Univ, Med Ctr, Sylvius Labs, Dept Human & Clin Genet, POB 9503, NL-2300 RA Leiden, Netherlands Leiden Univ POB 9503 Leiden Netherlands NL-2300 RA rlands
Citazione:
M.P.J. de Winther et al., "Transgenic mouse models to study the role of the macrophage scavenger receptor class A in atherosclerosis", INT J TISS, 22(2-3), 2000, pp. 85-91

Abstract

Several in vivo studies have been performed on the role of the macrophage scavenger receptor class A (SR-A) in atherosclerosis using SR-A knockout mice. The results indicate both an antiatherogenic and a proatherogenic role of SR-A, depending on the nature of the animal model serving as the athero-susceptible background. To study the role of SR-A in a different model, we generated a transgenic mouse model with high level expression of the human SR-A gene using a 180 Kb yeast artificial chromosome (MSR1 transgenic mice). These mice show increased expression of SR-A according to the natural expression pattern. The MSR1 transgenic mice were crossed onto a low-density lipoprotein receptor deficient background and were fed a high fat diet for 10 weeks. After this period, the size of the atherosclerotic lesions in the proximal aorta was measured. Surprisingly atherosclerosis was significantlyreduced in the MSR1 transgenic mice. In a second study the effect of SR-A was examined in APOE-3 Leiden mice providing a different athero-susceptiblebackground. To exclude nonmacrophage effects, bone marrow was transplantedfrom MSR1 mice and wildtype littermates to APOE-3 Leiden transgenic mice. After 8 weeks on a high fat diet, atherosclerosis in the mice that had received MSR1 bone marrow was reduced compared with mice that had received wild-type bone marrow. This difference reached statistical significance when individual cholesterol exposure of the mice was taken into account. Both experiments indicated an antiatherogenic role of the SR-A. This observation cannot be explained easily by SR-A function in foam cell formation because in MSR1 macrophages in vitro foam cell formation is increased. Alternatively: however; SR-A may affect the activation of macrophages. Hence the response to lipopolysaccharide was measured in MSR1-transgenic macrophages. These macrophages showed a reduction,in their activation in response to lipopolysaccharide, as measured by nitric oxide production. These data show that an elevated level of SR-A expression reduces atherosclerosis, potentially by modifying the response of macrophages to activation signals in the plaque.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/05/20 alle ore 07:29:13