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Titolo:
beta(2)-adrenergic receptor overexpression driven by alpha-MHC promoter isdownregulated in hypertrophied and failing myocardium
Autore:
Sheridan, DJ; Autelitano, DJ; Wang, BH; Percy, E; Woodcock, EA; Du, XJ;
Indirizzi:
Baker Med Res Inst, Melbourne, Vic 8008, Australia Baker Med Res Inst Melbourne Vic Australia 8008 urne, Vic 8008, Australia
Titolo Testata:
CARDIOVASCULAR RESEARCH
fascicolo: 1, volume: 47, anno: 2000,
pagine: 133 - 141
SICI:
0008-6363(200007)47:1<133:BRODBA>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
MYOSIN HEAVY-CHAIN; CARDIAC-SPECIFIC OVEREXPRESSION; NECROSIS-FACTOR-ALPHA; TRANSGENIC MICE; DILATED CARDIOMYOPATHY; GENE-EXPRESSION; CONTRACTILE FAILURE; HEART-FAILURE; HYPERPLASIA; ACTIVATION;
Keywords:
gene expression; heart failure; hypertrophy; receptors;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Du, XJ Baker Med Res Inst, POB 6492,St Kilda Rd Cent, Melbourne, Vic 8008,Australia Baker Med Res Inst POB 6492,St Kilda Rd Cent Melbourne Vic Australia 8008
Citazione:
D.J. Sheridan et al., "beta(2)-adrenergic receptor overexpression driven by alpha-MHC promoter isdownregulated in hypertrophied and failing myocardium", CARDIO RES, 47(1), 2000, pp. 133-141

Abstract

Objective: The a-myosin heavy chain (alpha-MHC) promoter is frequently used to direct cardiac specific transgene expression. We studied whether transgene expression controlled by this promoter was altered under conditions ofcardiac hypertrophy and failure. Methods: Transgenic (TG) mice overexpressing human beta(2)-adrenergic receptors (P,AR) and wild type (WT) controls were subjected to thoracic aortic constriction (TAC) or sham operation and studied at I, 3 and 8 weeks after surgery. Results: Sham operated TG mice had higher heart rates and left ventricular (LV) contractility than WT (all P<0.01), demonstrating enhanced PAR activation. TAC at 1, 3 and 8 weeks produced progressive LV hypertrophy which was similar between WT and TG mice. Evidence of heart failure was more marked in TG mice with a greater increasein weights of the right ventricle and lungs and a higher prevalence of atrial thrombus (P<0.05 in each case). In hypertrophied TG hearts, endogenous alpha-MHC mRNA transcripts in LV were maintained at 1 and 3 weeks, but werereduced by approximately 40% relative to the sham-operated group at 8 weeks after TAG. Transgene expression, measured as human beta(2)AR mRNA, was reduced by 45% at 1 and 3 weeks and by 70% at 8 weeks after TAG. beta(2)AR binding sites were reduced by 35, 47 and 65%, respectively, at 1, 3 and 8 weeks. Conclusion: Cardiac hypertrophy and failure cause downregulation of theendogenous alpha-MHC as well as cardiac specific overexpression of the transgene directed by an alpha-MHC promoter. (C) 2000 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 16:59:55