Antibody therapy can enhance AngiotensinII-induced myocardial fibrosis

Nicole L. Rosin, Alison J. Gareau, Devin Betsch, Alec Falkenham, Mryanda J. Sopel, Timothy D.G. Lee, Jean Francois Légaré

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Myocardial fibrosis is a pathological process that is characterized by disrupted regulation of extracellular matrix proteins resulting in permanent scarring of the heart tissue and eventual diastolic heart failure. Pro-fibrotic molecules including transforming growth factor-β and connective tissue growth factor are expressed early in the AngiotensinII (AngII)-induced and other models of myocardial fibrosis. As such, antibody-based therapies against these and other targets are currently under development. Results: In the present study, C57Bl/6 mice were subcutaneously implanted with a mini-osmotic pump containing either AngII (2.0 μg/kg/min) or saline control for 3 days in combination with mIgG (1 mg/kg/d) injected through the tail vein. Fibrosis was assessed after picosirius red staining of myocardial cross-sections and was significantly increased after AngII exposure compared to saline control (11.37 ± 1.41%, 4.94 ± 1.15%; P <0.05). Non-specific mIgG treatment (1 mg/kg/d) significantly increased the amount of fibrosis (26.34 ± 3.03%; P <0.01). However, when AngII exposed animals were treated with a Fab fragment of the mIgG or mIgM, this exacerbation of fibrosis was no longer observed (14.49 ± 2.23%; not significantly different from AngII alone).Conclusions: These data suggest that myocardial fibrosis was increased by the addition of exogenous non-specific antibodies in an Fc-mediated manner. These findings could have substantial impact on the future experimental design of antibody-based therapeutics.

Original languageEnglish (US)
Article number6
JournalFibrogenesis and Tissue Repair
Volume7
Issue number1
DOIs
StatePublished - Apr 10 2014
Externally publishedYes

Keywords

  • AngiotensinII
  • Antibody
  • Collagen
  • Inflammation
  • Myocardial fibrosis

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Rheumatology
  • Hepatology
  • Dermatology
  • Gastroenterology

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