title: Effects of zinc oxide nanoparticles on human coronary artery endothelial cells.
abstract: Inhalation of zinc oxide (ZnO) metal fumes is known to cause metal fume fever and to have systemic effects; however, the effects of ZnO nanoparticles (ZnONPs) on the cardiovascular system remain unclear. The objective of this study was to investigate the cardiovascular toxicity of ZnONPs. Human coronary artery endothelial cells (HCAECs) were exposed to ZnONPs of different sizes to investigate the cell viability, 8-hydroxy-2'-deoxyguanosine (8-OHdG), interleukin (IL)-6, nitric oxide (NO), and regulation of cardiovascular disease-related genes. Exposure of HCAECs to ZnONPs resulted in decreased cell viability and increased levels of 8-OHdG, IL-6, and NO. Downregulation of cardiovascular-associated genes was observed in response to ZnONPs in HCAECs determined by qPCR, suggesting that the calcium signaling pathway, neuroactive ligand-receptor interaction, hypertrophic cardiomyopathy, dilated cardiomyopathy, and renin-angiotensin system are important affected pathways in response to ZnONPs. Furthermore, we observed a significant response of AGTR1 to ZnONP exposure in HCAECs. Our results suggest that ZnONPs cause toxicity to HCAECs, which could be associated with cardiovascular dysfunction.
authors.affiliation: School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan; Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: kjc@tmu.edu.tw.
authors.forename: Kai-Jen
authors.initials: KJ
authors.lastname: Chuang
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: kangyunlee68@gmail.com.
authors.forename: Kang-Yun
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Institute of Labor, Occupational Safety and Health, Ministry of Labor, New Taipei City, Taiwan; School of Public Health, National Defense Medical Center, Taipei, Taiwan. Electronic address: chpan@mail.iosh.gov.tw.
authors.forename: Chih-Hong
authors.initials: CH
authors.lastname: Pan
authors.affiliation: School of Public Health, National Defense Medical Center, Taipei, Taiwan. Electronic address: lgh@ndmctsgh.edu.tw.
authors.forename: Ching-Huang
authors.initials: CH
authors.lastname: Lai
authors.affiliation: Department of Internal Medicine, Division of Cardiology, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: hspenos@yahoo.com.tw.
authors.forename: Lian-Yu
authors.initials: LY
authors.lastname: Lin
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: shu-chuan@tmu.edu.tw.
authors.forename: Shu-Chuan
authors.initials: SC
authors.lastname: Ho
authors.affiliation: Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong; Shenzhen Municipal Key Laboratory for Health Risk Analysis, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China. Electronic address: kfho@cuhk.edu.hk.
authors.forename: Kin-Fai
authors.initials: KF
authors.lastname: Ho
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: r92841005@ntu.edu.tw.
authors.forename: Hsiao-Chi
authors.initials: HC
authors.lastname: Chuang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000032:analysis*; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D003879:Dermatologic Agents / Q000633:toxicity; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D053768:Metal Nanoparticles / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015034:Zinc Oxide / Q000633:toxicity*
chemical_list: C544065:AGTR1 protein, human; D015415:Biomarkers; D003879:Dermatologic Agents; C508600:IL6 protein, human; D015850:Interleukin-6; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D009569:Nitric Oxide; D015034:Zinc Oxide; D002118:Calcium
keywords: AGTR1; Inflammation; Nanoparticles; Nitric oxide; Oxidative stress