Adenovirus-mediated delivery of relaxin reverses cardiac fibrosis

被引：39

作者：

Bathgate, R. A. D. ^{[1
]}

Lekgabe, E. D. ^{[1
,2
,3
]}

McGuane, J. T. ^{[1
]}

Su, Y. ^{[3
]}

Pham, T. ^{[3
]}

Ferraro, T. ^{[1
]}

Layfield, S. ^{[1
]}

Hannan, R. D. ^{[2
,4
]}

Thomas, W. G. ^{[3
]}

Samuel, C. S. ^{[1
,2
]}

Du, X. -J. ^{[3
]}

机构：

[1] Univ Melbourne, Howard Florey Inst, Melbourne, Vic 3010, Australia

[2] Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic 3052, Australia

[3] Baker Heart Res Inst, Melbourne, Vic 8008, Australia

[4] Peter MacCallum Canc Ctr, Melbourne, Vic 3002, Australia

来源：

MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2008年 / 280卷 / 1-2期

基金：

英国医学研究理事会;

关键词：

relaxin; RXFP1; fibrosis; extracellular matrix; adenovirus; gene therapy;

D O I：

10.1016/j.mce.2007.09.008

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

We have evaluated the effectiveness of systemic adenovirally delivered mouse relaxin on reversing fibrosis in a transgenic murine model of fibrotic cardiomyopathy due to beta(2)-adrenergic receptor (beta(2)AR) overexpression. Recombinant adenoviruses expressing green fluorescent protein (Ad-GFP), rat relaxin (Ad-rRLN) and mouse relaxin (Ad-mRLN) were generated and Ad-rRLN and Ad-mRLN were demonstrated to direct the expression of bioactive relaxin peptides in vitro. A single systemic injection of Ad-mRLN resulted in transgene expression in the liver and bioactive relaxin peptide in the plasma. Ad-mRLN, but not Ad-GFP, treatment reversed the increased left ventricular collagen content in beta(2)AR mice to control levels without affecting collagen levels in other heart chambers or in the lung and kidney. Hence a single systemic injection of adenovirus producing mouse relaxin reverses cardiac fibrosis without adversely affecting normal collagen levels in other organs and establishes the potential for the use of relaxin gene therapy for the treatment of cardiac fibrosis. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

引用

页码：30 / 38

页数：9

共 45 条

[1] Purification and characterization of relaxin from the tammar wallaby (Macropus eugenii):: Bioactivity and expression in the corpus luteum [J].

Bathgate, RAD ;

Siebel, AL ;

Tovote, P ;

Claasz, A ;

Macris, M ;

Tregear, GW ;

Parry, LJ .

BIOLOGY OF REPRODUCTION, 2002, 67 (01) :293-300

[2]

BATHGATE RAD, 2006, PHYSL REPROD, P679

[3]

Beck C, 2004, CURR GENE THER, V4, P457

[4]

Blomer U, 1997, J VIROL, V71, P6641

[5] Increased expression of UBF is a critical determinant for rRNA synthesis and hypertrophic growth of cardiac myocytes [J].

Brandenburger, Y ;

Jenkins, A ;

Autelitano, DJ ;

Hannan, RD .

FASEB JOURNAL, 2001, 15 (09) :2051-+

[6] Adenovirus-mediated regulable target gene expression in vivo [J].

Burcin, MM ;

Schiedner, G ;

Kochanek, S ;

Tsai, SY ;

O'Malley, BW .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (02) :355-360

[7] Preserved ventricular contractility in infarcted mouse heart overexpressing β2-adrenergic receptors [J].

Du, XJ ;

Gao, XM ;

Jennings, GL ;

Dart, AM ;

Woodcock, EA .

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2000, 279 (05) :H2456-H2463

[8] Age-dependent cardiomyopathy and heart failure phenotype in mice overexpressing β2-adrenergic receptors in the heart [J].

Du, XJ ;

Gao, XM ;

Wang, BH ;

Jennings, GL ;

Woodcock, EA ;

Dart, AM .

CARDIOVASCULAR RESEARCH, 2000, 48 (03) :448-454

[9] Increased myocardial collagen and ventricular diastolic dysfunction in relaxin deficient mice: a gender-specific phenotype [J].

Du, XJ ;

Samuel, CS ;

Gao, XM ;

Zhao, L ;

Parry, LJ ;

Tregear, GW .

CARDIOVASCULAR RESEARCH, 2003, 57 (02) :395-404

[10] β2-adrenergic receptor overexpression exacerbates development of heart failure after aortic stenosis [J].

Du, XJ ;

Autelitano, DJ ;

Dilley, RJ ;

Wang, BH ;

Dart, AM ;

Woodcock, EA .

CIRCULATION, 2000, 101 (01) :71-77

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