論文 - 詳細
| RRC ID | 51683 |
|---|---|
| 著者 | Sakai S, Maruyama H, Kimura T, Tajiri K, Honda J, Homma S, Aonuma K, Miyauchi T. |
| タイトル | Antagonists to endothelin receptor type B promote apoptosis in human pulmonary arterial smooth muscle cells. |
| ジャーナル | Life Sci |
| Abstract |
AIMS:Vascular remodeling results from aberrations in the balance between cell proliferation and death, which is seen in the obstructive vasculature of pulmonary arterial hypertension (PAH). Endothelin (ET)-1 has a potent proliferative activity on vascular smooth muscle cells, and ET receptor inhibitors are used to treat PAH; however, it remains unclear whether ET receptor inhibition contributes to the apoptosis of pulmonary arterial smooth muscle cells (PASMCs), another cause of pulmonary vascular remodeling. MAIN METHODS:Cultured human PASMCs were treated with the ETA receptor antagonist BQ-123 (100μM), or the ETB antagonist A-192621 (1-100μM) or BQ-788 (1-100μM) for 48h. The cells were then incubated for another 24h with or without doxorubicin (DOX, 1μM), an anthracyclin antitumor antibiotic that promotes p53-mediated apoptosis. Cell viability and apoptosis were evaluated by MTT assays, caspase-3/7 activity assays, and Western blots for cleaved caspase-3 expression. KEY FINDINGS:The viability of PASMCs was significantly decreased by A-192621 and BQ-788, in a dose-dependent manner. A-192621 and BQ-788 significantly increased the caspase-3/7 activity and cleaved caspase-3 expression in PASMCs. The PASMCs' susceptibility to DOX-induced apoptosis was significantly higher in the presence of A-192621 and BQ-788 than with vehicle. However, BQ-123 did not affect these parameters. SIGNIFICANCE:Blockade of the ETB receptor increases the extent of apoptosis and susceptibility to DOX-induced apoptosis in PASMCs. Apoptosis caused by ETB receptor blockade in PASMCs may be one of the mechanisms by which vascular remodeling is reduced in ET receptor inhibitor-based PAH treatments. |
| 巻・号 | 159 |
| ページ | 116-120 |
| 公開日 | 2016-8-15 |
| DOI | 10.1016/j.lfs.2016.03.044 |
| PII | S0024-3205(16)30193-X |
| PMID | 27021787 |
| MeSH | Apoptosis / drug effects* Caspase 3 / metabolism Caspase 7 / metabolism Cells, Cultured Endothelin Receptor Antagonists / pharmacology* Humans Muscle, Smooth, Vascular / cytology* Muscle, Smooth, Vascular / enzymology Muscle, Smooth, Vascular / metabolism Pulmonary Artery / cytology* Pulmonary Artery / enzymology Pulmonary Artery / metabolism Receptor, Endothelin B / drug effects* |
| IF | 3.647 |
| 引用数 | 4 |
| リソース情報 | |
| ヒト・動物細胞 | GI-1(RCB0763) |