| First Author | Li X | Year | 2022 |
| Journal | Exp Cell Res | Volume | 419 |
| Issue | 1 | Pages | 113300 |
| PubMed ID | 35926661 | Mgi Jnum | J:328249 |
| Mgi Id | MGI:7335779 | Doi | 10.1016/j.yexcr.2022.113300 |
| Citation | Li X, et al. (2022) Loss of alpha7nAChR enhances endothelial-to-mesenchymal transition after myocardial infarction via NF-kappaB activation. Exp Cell Res 419(1):113300 |
| abstractText | The myocardial fibrosis in response to myocardial infarction (MI) is closely related to the dysbalance of endothelial-to-mesenchymal transition (EndMT). Although numerous reports indicate that alpha7 nicotinic acetylcholine receptor (alpha7nAChR) activates the cholinergic anti-inflammatory pathway (CAP) to regulate the magnitude of inflammatory responses, the role of alpha7nAChR in myocardial fibrosis, as well as the underlying mechanisms, have not been elucidated. In this study, we evaluated cardiac function, fibrosis, and EndMT signaling using a mouse model of MI and interleukin (IL)-1beta-induced human cardiac microvascular endothelial cells (HCMECs). In vivo, alpha7nAChR deletion increased cardiac dysfunction, exacerbated the cardiac inflammatory response, and NF-kappaB activation, and enhanced EndMT, as shown by higher expression levels of fibroblast markers (FSP-1, alpha-SMA, collagen I, Snail) and decreased levels of the FGFR1, glucocorticoid receptor (GR) and endothelial marker (CD31) compared to wild-type mice. In vitro, the pharmacological activation of alpha7nAChR with PNU282987 significantly inhibited IL-1beta-induced EndMT, as shown by a reduced transition to the fibroblast-like phenotype and the expression of fibrotic markers. Moreover, the IL-1beta-mediated activation of NF-kappaB pathway was suppressed by PNU282987. This anti-EndMT effect of alpha7nAChR was associated with regulation of Snail. Furthermore, Western blot analysis further revealed that the GR antagonist RU38486 could partially counteract the effect of PNU282987 on NF-kappaB expression. In conclusion, our results show that alpha7nAChR is involved in cardiac fibrosis by inhibiting EndMT, providing a novel approach to the treatment of MI. |
