Anesthetic propofol overdose causes vascular hyperpermeability by reducing endothelial glycocalyx and ATP production

Ming Chung Lin, Chiou-Feng Lin, Chien Feng Li, Ding Ping Sun, Li Yun Wang, Chung-Hsi Hsing

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)12092-12107
Number of pages16
JournalInternational Journal of Molecular Sciences
Volume16
Issue number6
DOIs
Publication statusPublished - May 27 2015

Fingerprint

anesthetics
Glycocalyx
Anesthetics
adenosine triphosphate
Adenosinetriphosphate
Propofol
Blood Vessels
Adenosine Triphosphate
Endothelial cells
Syndecan-4
NAD
causes
Glypicans
sulfates
Syndecan-1
Cytotoxicity
Heparitin Sulfate
nicotinamide
adenines
Messenger RNA

Keywords

  • ATP
  • Endothelial cells
  • Glycocalyx
  • Mice
  • Propofol
  • Vascular permeability

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Inorganic Chemistry
  • Catalysis
  • Molecular Biology
  • Computer Science Applications

Cite this

Anesthetic propofol overdose causes vascular hyperpermeability by reducing endothelial glycocalyx and ATP production. / Lin, Ming Chung; Lin, Chiou-Feng; Li, Chien Feng; Sun, Ding Ping; Wang, Li Yun; Hsing, Chung-Hsi.

In: International Journal of Molecular Sciences, Vol. 16, No. 6, 27.05.2015, p. 12092-12107.

Research output: Contribution to journalArticle

Lin, Ming Chung ; Lin, Chiou-Feng ; Li, Chien Feng ; Sun, Ding Ping ; Wang, Li Yun ; Hsing, Chung-Hsi. / Anesthetic propofol overdose causes vascular hyperpermeability by reducing endothelial glycocalyx and ATP production. In: International Journal of Molecular Sciences. 2015 ; Vol. 16, No. 6. pp. 12092-12107.
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