Key result
Non-specific mIgG increases Angiotensin II-induced myocardial fibrosis by ~132%, an effect prevented by Fab fragments.
Why the study?
Antibody-based therapies targeting pro-fibrotic molecules are under development for myocardial fibrosis, but their effects in AngiotensinII-induced fibrosis models require investigation.
Does non-specific antibody therapy exacerbate Angiotensin II-induced myocardial fibrosis in mice?
Does non-specific antibody therapy exacerbate Angiotensin II-induced myocardial fibrosis in mice?
Exogenous non-specific antibodies can exacerbate Angiotensin II-induced myocardial fibrosis in an Fc-mediated manner, which may impact the design of antibody-based therapeutics.
Answers are grounded in this paper and cite their sources.
Alerts to fibrosis risk with non-specific antibodies; hypothesis-generating for Fc-engineered designs in cardiac therapeutics.
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.
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Rosin et al. (2014) studied Myocardial fibrosis (n=31). Non-specific mouse IgG (mIgG) vs. Angiotensin II alone was evaluated on Myocardial fibrosis area (%) (p=<0.01). Administration of non-specific mIgG significantly increased Angiotensin II-induced myocardial fibrosis from 11.37% to 26.34% (P <0.01), an effect that was prevented by using Fab fragments.
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