Adenovirus-mediated delivery of relaxin reverses cardiac fibrosis

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:280

Article

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 

[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

关键词: relaxin;    RXFP1;    fibrosis;    extracellular matrix;    adenovirus;    gene therapy;   

DOI  :  10.1016/j.mce.2007.09.008

来源: Elsevier

【 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.

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