title: Qiliqiangxin protects against anoxic injury in cardiac microvascular endothelial cells via NRG-1/ErbB-PI3K/Akt/mTOR pathway.
abstract: Cardiac microvascular endothelial cells (CMECs) are important angiogenic components and are injured rapidly after cardiac ischaemia and anoxia. Cardioprotective effects of Qiliqiangxin (QL), a traditional Chinese medicine, have been displayed recently. This study aims to investigate whether QL could protect CMECs against anoxic injury and to explore related signalling mechanisms. CMECs were successfully cultured from Sprague-Dawley rats and exposed to anoxia for 12 hrs in the absence and presence of QL. Cell migration assay and capillary-like tube formation assay on Matrigel were performed, and cell apoptosis was determined by TUNEL assay and caspase-3 activity. Neuregulin-1 (NRG-1) siRNA and LY294002 were administrated to block NRG-1/ErbB and PI3K/Akt signalling, respectively. As a result, anoxia inhibited cell migration, capillary-like tube formation and angiogenesis, and increased cell apoptosis. QL significantly reversed these anoxia-induced injuries and up-regulated expressions of NRG-1, phospho-ErbB2, phospho-ErbB4, phospho-Akt, phospho-mammalian target of rapamycin (mTOR), hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in CMECs, while NRG-1 knockdown abolished the protective effects of QL with suppressed NRG-1, phospho-ErbB2, phospho-ErbB4, phospho-Akt, phospho-mTOR, HIF-1α and VEGF expressions. Similarly, LY294002 interrupted the beneficial effects of QL with down-regulated phospho-Akt, phospho-mTOR, HIF-1α and VEGF expressions. However, it had no impact on NRG-1/ErbB signalling. Our data indicated that QL could attenuate anoxia-induced injuries in CMECs via NRG-1/ErbB signalling which was most probably dependent on PI3K/Akt/mTOR pathway.
authors.affiliation: Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Jingmin
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Chunjie
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Fu
authors.affiliation: Department of Cardiology, Shandong University, Jinan, Shandong, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Xueting
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Cardiology, People's Hospital of Nanbu County, Nanchong, Sichuan, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.affiliation: Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D008297:Male; D055806:Microvessels / Q000473:pathology*; D009025:Morpholines / Q000494:pharmacology; D009206:Myocardium / Q000473:pathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D020890:Neuregulin-1 / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D053148:Caspase 3; D002867:Chromones; D004365:Drugs, Chinese Herbal; D009025:Morpholines; D020890:Neuregulin-1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases; C572413:qiliqiangxin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: 
  Qiliqiangxin
  ; angiogenesis; anoxia; apoptosis; cardiac microvascular endothelial cell; neuregulin