Macrophages Aggravate Hypoxia-Induced Cardiac Microvascular Endothelial Cell Injury via Peroxynitrite: Protection by Tongxinluo
Xiujuan Wang
Kun Liu
Bin Li
Yanning Li
Kaiwei Ye
Jinsheng Qi
Yu Wang
10.6084/m9.figshare.4315748.v2
https://tandf.figshare.com/articles/journal_contribution/Macrophages_Aggravate_Hypoxia-Induced_Cardiac_Microvascular_Endothelial_Cell_Injury_via_Peroxynitrite_Protection_by_Tongxinluo/4315748
<p>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.</p>
2018-11-29 08:41:42
Human cardiac microvascular endothelial cells
hypoxia
macrophage
peroxynitrite
tongxinluo