Abstract 17072: Acetylcholine Signaling and Endothelial to Mesenchymal Transition in Pulmonary Arterial Hypertension
| Autor: | Peng Zhang, Ana Fernandez Nicolas, Gaurav Choudhary, Alexander Vang, Richard T. Clements, Thomas Mancini, Denielli da Silva Goncalves Bos |
|---|---|
| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Circulation. 142 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/circ.142.suppl_3.17072 |
| Popis: | Introduction: Pulmonary arterial hypertension (PAH) is characterized by severe pulmonary vascular remodeling. Transition of endothelial cells (EC) to mesenchymal cells (EndMT) contributes to vascular remodeling; however, the role of EndMT and underlying mechanisms in PAH remain unclear. While nicotinic acetylcholine (Ach) receptor (nAChR)-mediated pathway regulates epithelial to mesenchymal transition and promotes mesenchymal cell proliferation, its role in EndMT is unknown. In this study, we investigate EndMT in PAH and delineate the mechanisms. Methods: PAH was induced in Sprague Dawley rats by SU5416 (20 mg/kg; s.c.), followed by 3 wks of hypoxia (3 wk PAH) or 3wks of hypoxia with additional 4 wks of normoxia (7 wk PAH). Rats without SU5416 and kept at normoxia served as controls. At the end of experiments, hemodynamic measurements were performed. Lung EC were then isolated and purified using CD31 antibody conjugated beads and passage 3-4 were used. EndMT was assessed by dual staining of EC markers (von Willebrand factor and Griffonia simplicifolia) and α-smooth muscle actin (α-SMA) and by the mRNA expression of EC and mesenchymal genes. Lung ACh was measured by ELISA. Results: PAH rats had elevated PA pressures at both 3 wk (PAH vs. CON in mm Hg: 77.3 vs. 24.8, pIn vitro , treatment with ACh markedly induced EndMT in lung EC from normal rats, which was assessed by increased dual staining of EC markers and α-SMA and increased expression of mesenchymal genes (α-SMA, PAI1, and pro-collagen 1, p Conclusions: EndMT in PAH is associated with increased lung ACh levels and α7nAChR expression in lung ECs. ACh/nAChR-mediated EndMT may contribute to the vascular remodeling in PAH. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|