Abstract P166: Paracrine Endothelial Microrna214 Exosomes Modulate Smooth Muscle Cell Function in Pulmonary Arterial Hypertension
| Autor: | Patrick J. Pagano, Sanghamitra Sahoo |
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| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Hypertension. 74 |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hyp.74.suppl_1.p166 |
| Popis: | Background: Communication among various cell types is known to play a pivotal role in PAH. Endothelial cell (EC)-derived exosomes have emerged as important mediators of intercellular communication and are known to influence the function of recipient cells. A role for miR-214 in EC-derived exosomes in PAH, however, is entirely unknown. In this study, we hypothesize that hypoxia-induced EC injury releases exosomes enriched in miR-214 that mediates phenotype switching of smooth muscle cells (SMCs) resulting in increased SMC proliferation in PAH. Methods and Results: We subjected human pulmonary artery endothelial cells (hPAECs) to hypoxia vs. normoxia (norm) to recapitulate the PAH phenotype in vitro . Quantitative RT-PCR of hPAECs showed that hypoxia upregulated miR-214 by 1.51±0.24-fold (pp p p =0.05). Conclusions & Discussion: We found that miR-214 expression was induced in hypoxia both in ECs and in exosomes released from them. Furthermore, EC-derived hypoxic or miR-214-laden exosomes were able to transduce changes in SMC, which result in a proliferative and synthetic phenotype. These findings demonstrate that EC-derived miR-214 can direct a proliferative fate for smooth muscle cells, and may contribute to SMC-associated pathophysiological changes in PAH. |
| Databáze: | OpenAIRE |
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