title: Anesthetic propofol overdose causes vascular hyperpermeability by reducing endothelial glycocalyx and ATP production.
abstract: Prolonged treatment with a large dose of propofol may cause diffuse cellular cytotoxicity; however, the detailed underlying mechanism remains unclear, particularly in vascular endothelial cells. Previous studies showed that a propofol overdose induces endothelial injury and vascular barrier dysfunction. Regarding the important role of endothelial glycocalyx on the maintenance of vascular barrier integrity, we therefore hypothesized that a propofol overdose-induced endothelial barrier dysfunction is caused by impaired endothelial glycocalyx. In vivo, we intraperitoneally injected ICR mice with overdosed propofol, and the results showed that a propofol overdose significantly induced systemic vascular hyperpermeability and reduced the expression of endothelial glycocalyx, syndecan-1, syndecan-4, perlecan mRNA and heparan sulfate (HS) in the vessels of multiple organs. In vitro, a propofol overdose reduced the expression of syndecan-1, syndecan-4, perlecan, glypican-1 mRNA and HS and induced significant decreases in the nicotinamide adenine dinucleotide (NAD+)/NADH ratio and ATP concentrations in human microvascular endothelial cells (HMEC-1). Oligomycin treatment also induced significant decreases in the NAD+/NADH ratio, in ATP concentrations and in syndecan-4, perlecan and glypican-1 mRNA expression in HMEC-1 cells. These results demonstrate that a propofol overdose induces a partially ATP-dependent reduction of endothelial glycocalyx expression and consequently leads to vascular hyperpermeability due to the loss of endothelial barrier functions.
authors.affiliation: Department of Anesthesiology, Chi Mei Medical Center, Liouying, 201, Taikang, Taikang Village, Liuying District, Tainan 736, Taiwan. mygegon@gmail.com.|Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, 89, Wenhwa 1st Street, Rende District, Tainan 717, Taiwan. mygegon@gmail.com.
authors.forename: Ming-Chung
authors.initials: MC
authors.lastname: Lin
authors.affiliation: Department of Microbiology and Immunology, Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei 110, Taiwan. cflin2014@tmu.edu.tw.
authors.forename: Chiou-Feng
authors.initials: CF
authors.lastname: Lin
authors.affiliation: Department of Pathology, Chi Mei Medical Center, 901 Zhonghua Road, Yongkang District, Tainan 710, Taiwan. angelo.p@yahoo.com.tw.
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Li
authors.affiliation: Department of Surgery, Chi Mei Medical Center, 901 Zhonghua Road, Yongkang District, Tainan 710, Taiwan. sdp0127@yahoo.com.tw.
authors.forename: Ding-Ping
authors.initials: DP
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Chi Mei Medical Center, 901 Zhonghua Road, Yongkang District, Tainan 710, Taiwan. sindysea@hotmail.com.
authors.forename: Li-Yun
authors.initials: LY
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Chi Mei Medical Center, 901 Zhonghua Road, Yongkang District, Tainan 710, Taiwan. hsing@mail.chimei.org.tw.|Department of Anesthesiology, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei 110, Taiwan. hsing@mail.chimei.org.tw.
authors.forename: Chung-Hsi
authors.initials: CH
authors.lastname: Hsing
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000777:Anesthetics / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002460:Cell Line; D002478:Cells, Cultured; D004195:Disease Models, Animal; D062787:Drug Overdose / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D042783:Endothelial Cells / Q000187:drug effects; D005786:Gene Expression Regulation; D019276:Glycocalyx / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015742:Propofol / Q000008:administration & dosage / Q000633:toxicity*; D053667:Syndecans / Q000235:genetics / Q000378:metabolism
chemical_list: D000777:Anesthetics; D053667:Syndecans; D000255:Adenosine Triphosphate; D015742:Propofol
keywords: ATP; endothelial cells; glycocalyx; mice; propofol; vascular permeability