title: Macrophages Aggravate Hypoxia-Induced Cardiac Microvascular Endothelial Cell Injury via Peroxynitrite: Protection by Tongxinluo.
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.
authors.affiliation: a Department of Biochemistry, Hebei Key Laboratory of Medical Biotechnology , Hebei Medical University , Shijiazhuang , P.R. China.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: a Department of Biochemistry, Hebei Key Laboratory of Medical Biotechnology , Hebei Medical University , Shijiazhuang , P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Liu
authors.affiliation: a Department of Biochemistry, Hebei Key Laboratory of Medical Biotechnology , Hebei Medical University , Shijiazhuang , P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: b Department of Molecular Biology Hebei Key Lab of Laboratory Animal , Hebei Medical University , Shijiazhuang , P.R. China.
authors.forename: Yanning
authors.initials: Y
authors.lastname: Li
authors.affiliation: a Department of Biochemistry, Hebei Key Laboratory of Medical Biotechnology , Hebei Medical University , Shijiazhuang , P.R. China.
authors.forename: Kaiwei
authors.initials: K
authors.lastname: Ye
authors.affiliation: a Department of Biochemistry, Hebei Key Laboratory of Medical Biotechnology , Hebei Medical University , Shijiazhuang , P.R. China.
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Qi
authors.affiliation: b Department of Molecular Biology Hebei Key Lab of Laboratory Animal , Hebei Medical University , Shijiazhuang , P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
mesh_terms: D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D051546:Cyclooxygenase 2 / Q000378:metabolism; D019610:Cytoprotection; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D008264:Macrophages / Q000187:drug effects*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D042461:Vascular Endothelial Growth Factor A; C513941:tongxinluo; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2
keywords: Human cardiac microvascular endothelial cells; hypoxia; macrophage; peroxynitrite; tongxinluo