Adenovirus-mediated delivery of relaxin reverses cardiac fibrosis

Ross Bathgate, Edna Lekgabe, J McGuane, Y Su, Tam Pham, Tania Ferraro, Sharon Layfield, Ross Hannan, Walter Thomas, Chrishan Samuel, Xiao-Jun Du

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37 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)30 - 38
Number of pages9
JournalMolecular and Cellular Endocrinology
Volume280
Issue number1-2
DOIs
Publication statusPublished - 2008
Externally publishedYes

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