Abstract 19530: Cardiac Fibroblasts Derived Exosomes Enhanced Endothelial to Mesenchymal Transition and Associated Fibrotic Signaling
Background: Endothelial to mesenchymal transition (EndMT), play critical role in pressure overload-induced pathological fibrosis. Recent studies suggested the contribution of fibroblasts-derived exosomes in pressure overload (PO)-induced cardiac fibrosis. Here we investigated whether fibroblasts-derived exosomes play significant role on pressure overload-induced EndMT.
Methods and Results: Cardiac fibroblasts were isolated from neonatal rat heart and treated with Ang II for 48hs. At the end of treatment, culture media were collected to isolate exosomes using ultracentrifugation method. To initiate EndMT, both mouse heart endothelial cells and HUVECs were exposed with Ang II and PBS treated exosome. Ang II-exosome treated cells showed enhanced vimentin/FSP1 immuno-staining as compared to PBS exosomes. Furthermore, Ang II-exosomes treatment significantly increased both profibrotic RNAs (collagen 1a, TGF-b, ANP and BNP) and proteins (pSmad, a-Smooth muscle actin) expressions. Microarray analysis of Ang II-exosomal contents showed increased accumulation of profibrotic miRNAs.
Conclusion: Taken together, these preliminary results suggest that fibroblasts-derived exosomes are enriched in pro-fibrotic miRNAs and can lead to endothelial to mesenchymal transition and associated fibrosis in pressure-overloaded myocardium. Ongoing in vitro and in vivo investigations, will provide better understanding for the mechanistic and therapeutic aspects of exosome on PO-induced cardiac fibrosis and remodeling.
Author Disclosures: S.K. Verma: None. V.N. Girikipathi: None. M. Khan: None. C. Benedict: None. E. Nickoloff: None. D. Goukassian: None. R. Kishore: None.
- © 2016 by American Heart Association, Inc.