Xiujuan Wang, Kun Liu, Bin Li, Yanning Li, Kaiwei Ye, J. Qi, Yu Wang
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引用次数: 10
Abstract
Abstract Activated macrophages contribute to endothelial dysfunction; however, it is unclear how peroxynitrite contributes to macrophage-mediated human cardiac microvascular endothelial cell (HCMEC) injury in hypoxia. In macrophage-HCMEC co-cultures subjected to hypoxia, there was an increase in hypoxia-inducible factor (HIF)-1α, HIF-2α, inducible nitric oxide synthase (iNOS), endothelin-converting enzyme (ECE)-1 and cyclooxygenase-2 (COX-2), and concomitant decrease in prostacyclin synthase (PGIS). This was mimicked by a peroxynitrite donor and attenuated by its decomposition catalyst. Tongxinluo (TXL) could decrease HIF-2α, iNOS, ECE-1 and COX-2 and increase PGIS in a dose-dependent manner, with increase of vascular endothelial growth factor. The protein alterations verified the remarkably affected mRNAs, indicating that the effects of TXL were similar to but better than that of peroxynitrite decomposition catalyst. Furthermore, TXL inhibited macrophage-mediated nitrotyrosine accumulation and attenuated HCMEC injury. The results suggest that peroxynitrite contributes to macrophage-mediated HCMEC injury in hypoxia, and TXL attenuates HCMEC injury mainly by inhibiting peroxynitrite.
期刊介绍:
Cessation
Cell Communication and Adhesion is an international Open Access journal which provides a central forum for research on mechanisms underlying cellular signalling and adhesion. The journal provides a single source of information concerning all forms of cellular communication, cell junctions, adhesion molecules and families of receptors from diverse biological systems.
The journal welcomes submission of original research articles, reviews, short communications and conference reports.