title: IL-17 induces apoptosis of vascular endothelial cells: a potential mechanism for human acute coronary syndrome.
abstract: Th17 cells producing IL-17 are involved in the pathogenesis of atherosclerosis, but the underlying mechanisms remain unclear. In this study, we investigated the effects of IL-17 on human vascular endothelial cells and showed that IL-17 induced cell death of the vascular endothelial cells, which played a pivotal role in plaque destabilization triggering acute coronary syndrome (ACS). We showed that circulating Th17 cells and IL-17 increased in patients with ACS compared to the patients with stable angina or health individuals; the plasma levels of IL-6 increased but TGF-β decreased in ACS patients, exhibiting a positive and negative correlation with that of IL-17, respectively. Importantly, we uncovered that IL-17 promoted the production of von Willebrand factor by endothelial cells and induced endothelial apoptosis by activating caspase-3, caspase-9 and up-regulating the ratio of Bax/Bcl-2, indicating the function of IL-17 in vascular endothelial damage as a potential mechanism for the pathogenesis of human ACS.
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Faliang
authors.initials: F
authors.lastname: Zhu
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Chun
authors.initials: C
authors.lastname: Guo
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Xuelei
authors.initials: X
authors.lastname: Cao
authors.forename: Yongyu
authors.initials: Y
authors.lastname: Shi
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.forename: Chunhong
authors.initials: C
authors.lastname: Ma
authors.forename: Lining
authors.initials: L
authors.lastname: Zhang
mesh_terms: D054058:Acute Coronary Syndrome / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D060050:Angina, Stable / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000096:biosynthesis / Q000235:genetics; D053453:Caspase 9 / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D003324:Coronary Artery Disease / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D020381:Interleukin-17 / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D058504:Th17 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000097:blood; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics; D014841:von Willebrand Factor / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C494826:BAX protein, human; C508717:IL17A protein, human; C508600:IL6 protein, human; D020381:Interleukin-17; D015850:Interleukin-6; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D051028:bcl-2-Associated X Protein; D014841:von Willebrand Factor; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9