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

Lin MC, Lin CF, Li CF, Sun DP, Wang LY, Hsing CH - Int J Mol Sci (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Chi Mei Medical Center, Liouying, 201, Taikang, Taikang Village, Liuying District, Tainan 736, Taiwan. mygegon@gmail.com.

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.

No MeSH data available.


Related in: MedlinePlus

Propofol overdose effect on the relative expression of SDC-1, SDC-4 and PLC mRNA in the various organs of ICR mice. Propofol group mice were intraperitoneally-injected with 10 mg of PBS-diluted propofol within 5 h; the control group mice were injected with PBS only. The relative expression levels of SDC-1, SDC-4 and PLC mRNA of the various organs were detected using RT-PCR. The ratios to the untreated control are shown (means ± standard deviation of six mice). * p < 0.05 compared with the control group.
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ijms-16-12092-f002: Propofol overdose effect on the relative expression of SDC-1, SDC-4 and PLC mRNA in the various organs of ICR mice. Propofol group mice were intraperitoneally-injected with 10 mg of PBS-diluted propofol within 5 h; the control group mice were injected with PBS only. The relative expression levels of SDC-1, SDC-4 and PLC mRNA of the various organs were detected using RT-PCR. The ratios to the untreated control are shown (means ± standard deviation of six mice). * p < 0.05 compared with the control group.

Mentions: The relative expression levels of syndecan-1 and syndecan-4 mRNA in heart, blood vessel, lung, liver and kidney tissue and of perlecan mRNA in heart and lung tissue were significantly (p < 0.05) lower in the propofol group (Figure 2). Light microscopy after immunohistochemical (IHC) staining of the peritoneal vessel, lung and kidney tissue samples showed that HS was a component of the endothelial glycocalyx. In propofol mice, the endothelial cell lining was markedly less stained (Figure 3).


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

Lin MC, Lin CF, Li CF, Sun DP, Wang LY, Hsing CH - Int J Mol Sci (2015)

Propofol overdose effect on the relative expression of SDC-1, SDC-4 and PLC mRNA in the various organs of ICR mice. Propofol group mice were intraperitoneally-injected with 10 mg of PBS-diluted propofol within 5 h; the control group mice were injected with PBS only. The relative expression levels of SDC-1, SDC-4 and PLC mRNA of the various organs were detected using RT-PCR. The ratios to the untreated control are shown (means ± standard deviation of six mice). * p < 0.05 compared with the control group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490431&req=5

ijms-16-12092-f002: Propofol overdose effect on the relative expression of SDC-1, SDC-4 and PLC mRNA in the various organs of ICR mice. Propofol group mice were intraperitoneally-injected with 10 mg of PBS-diluted propofol within 5 h; the control group mice were injected with PBS only. The relative expression levels of SDC-1, SDC-4 and PLC mRNA of the various organs were detected using RT-PCR. The ratios to the untreated control are shown (means ± standard deviation of six mice). * p < 0.05 compared with the control group.
Mentions: The relative expression levels of syndecan-1 and syndecan-4 mRNA in heart, blood vessel, lung, liver and kidney tissue and of perlecan mRNA in heart and lung tissue were significantly (p < 0.05) lower in the propofol group (Figure 2). Light microscopy after immunohistochemical (IHC) staining of the peritoneal vessel, lung and kidney tissue samples showed that HS was a component of the endothelial glycocalyx. In propofol mice, the endothelial cell lining was markedly less stained (Figure 3).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Chi Mei Medical Center, Liouying, 201, Taikang, Taikang Village, Liuying District, Tainan 736, Taiwan. mygegon@gmail.com.

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.

No MeSH data available.


Related in: MedlinePlus