Involvement of Hsp90 in the anti-fibrotic effect of novel engineered extracellular vesicles with therapeutic capacity


Lecue Costas, Elena


Fibrosis is a well-recognized cause of morbidity and mortality; in the United States it is estimated that 45% of deaths can be attributed to fibrotic disorders. Myocardial fibrosis is characterized by the accumulation of extracellular matrix proteins triggered by the cytokine Transforming Growth Factor β (TGF- β) that generates fibrosis. In the worst case, cardiac fibrosis can impair cardiac muscle function by reducing ejection fraction, diminishing electrical conductance, and ultimately lading to patient death. In this study, special emphasis is put on the chaperone Heat Shock Protein 90 (Hsp90) that regulates several processes involved in cardiac fibrosis and its correlation with major pro-fibrotic proteins after treatment with engineered extracellular vesicles. Extracellular vesicles (EVs) are bilayer lipid vesicles that cells release for intercellular communication. In this project we used EVs as a carrier of a novel anti-fibrotic therapy. To evaluate EVs capabilities as nanocarriers, we isolated EVs extracted from fluorescent NIH-3T3 with Hsp90. Furthermore, this study evaluates the gene and protein expression of Hsp90 and Hsp90β in TGFβ-activated fibroblasts before and after administration of therapeutic EVs, and correlations with major profibrotic genes such as collagen I, III and fibronectin. We conclude that Hsp90 and Hsp90β play a direct role in the progression of myocardial fibrosis and their expression variations indicate the importance of different types of EVs in the fibrotic process.



Villar Ramos, Ana Victoria
Fornaguera i Puigvert, Cristina


IQS SE - Undergraduate Program in Biotechnology