Decorin Role in Extracellular Vesicles Used to Prevent Post-Operative Atrial Fibrillation

Abstract

Postoperative atrial fibrillation (AF) affects one-third of patients following cardiac surgery, increasing the risk of stroke. Inflammation-driven atrial fibrosis contributes to postoperative AF. Our lab is investigating the use of extracellular vesicles (EVs) derived from human atrial explant cells to mitigate atrial fibrosis and prevent AF. While EVs have demonstrated protective effects, the underlying mechanisms remain incompletely understood. Recently, our proteomic analysis revealed that EVs are enriched in decorin, an extracellular matrix protein known for its antifibrotic properties. This study investigates whether decorin helps EVs reduce atrial fibrosis by inhibiting profibrotic pathways. This investigation involves a comparison between EVs that contain decorin and those depleted of it. My findings confirm that decorin is highly enriched in EVs and demonstrate that decorin treatment reduces fibroblast proliferation stimulated by TGF-β1. Additionally, DsiRNA knockdown depletes decorin from EVs, providing a model to assess its role. Decorin-enriched EVs significantly reduced cell proliferation compared to decorin-depleted EVs. This suggests that decorin plays a significant role in addition to other factors contributing to the antifibrotic effect of EVs.