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- W2022181520 abstract "Previously we have demonstrated that relaxin therapy using osmotic minipumps reverses fibrotic cardiomyopathy in rodent models of established fibrosis, including transgenic mice with cardiac-restricted overexpression of β2-adrenergic receptors (β2-TG). In this study, we extended our research by investigating the feasibility of adenoviral-mediated relaxin delivery. Recombinant adenoviruses with a green fluorescent protein (GFP) cassette producing bioactive rat and mouse relaxin peptides (Ad-rRLN, Ad-mRLN, Ad-GFP) were generated. Following amplification and purification the viruses were used to infect HEK-293T cells to characterize their ability to produce bioactive relaxin peptides in vitro. Media from HEK-293T cells infected with Ad-rRLN and Ad-mRLN demonstrated relaxin bioactivity whereas Ad-GFP infected cell media was inactive. The β2-TG mouse model was then used to test efficacy of Ad-mRLN gene therapy. Ad-mRLN together with Ad-GFP as negative control was injected via the tail vein of male and female β2-TG mice at a dose of 5 × 1010pfu. The presence of bioactive relaxin peptide was detected from plasma samples collected at 3-days after injection. Two-weeks post-treatment, the kidneys and hearts were collected and collagen content in the organs was determined by both hydroxyproline assay and quantitative histology. Compared with their wild-type littermates, left ventricular (LV) collagen content was significantly increased in both genders of β2-TG mice (p<0.05 vs non-TG littermates). Adenovirus mediated overexpression of murine relaxin, but not GFP, restored collagen content in the LV of β2-TG to a normal level without adversely affecting collagen levels in other chambers of the heart and organs. Hence, systemic adenoviral relaxin delivery can reverse cardiac fibrosis." @default.
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- W2022181520 date "2006-10-01" @default.
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- W2022181520 title "Adenovirus-mediated delivery of relaxin reverses cardiac fibrosis in mice with fibrotic cardiomyopathy" @default.
- W2022181520 doi "https://doi.org/10.1016/j.yjmcc.2006.06.033" @default.
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