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ANESTHETIC PHARMACOLOGY

Propofol Reduces Apoptosis and Up-Regulates Endothelial Nitric Oxide Synthase Protein Expression in Hydrogen Peroxide-Stimulated Human Umbilical Vein Endothelial Cells

Baohua Wang, MD, PhD^*, Tao Luo, MD^*, David Chen, PhD, and David M. Ansley, MD, FRCPC^*

From the Departments of *Anesthesiology, Pharmacology and Therapeutics, and Chemistry, University of British Columbia, Vancouver, British Columbia, Canada.

Address correspondence and reprint requests to David M. Ansley, MD, FRCPC, UBC Department of Anesthesiology, Pharmacology and Therapeutics, Room 3200, 3rd Floor, JPP, 910 West 10th Ave., Vancouver, BC V5Z 4E3, Canada. Address e-mail to david.ansley{at}vch.ca.

BACKGROUND: Vascular endothelial cells play an important role in maintaining cardiovascular homeostasis. Oxidative stress is a critical pathogenic factor in endothelial cell damage and the development of cardiovascular diseases. In this study we evaluated the effects of propofol on oxidative stress-induced endothelial cell insults and the role of serine–threonine kinase Akt modulation of endothelial nitric oxide synthase (eNOS) as a mechanism of protection.

METHODS: Human umbilical vein endothelial cells were used as the experimental model. Hydrogen peroxide (H₂O₂, 100 µM) was used as the stimulus of oxidative stress. Study groups included 1) control; 2) cells incubated with H₂O₂ alone; 3) cells incubated with propofol (50 µM) alone; or 4) cells pretreated with propofol 50 µM for 30 min then co-incubated with H₂O₂. Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Trypan blue dye exclusion test. Cell apoptosis was evaluated by Hoechst 33258 staining. Caspase-3 activity was determined by the colorimetric CaspACE^TM Assay System. Expressions of Akt, phospho-Akt, and eNOS were detected by Western blotting.

RESULTS: H₂O₂ decreased cell viability, induced apoptosis, and increased caspase-3 activity in human umbilical vein endothelial cells. Propofol significantly protected cells from H₂O₂-induced cell damage, apoptosis and decreased H₂O₂-induced increase in caspase-3 activity. Propofol treatment significantly increased eNOS expression compared to control and H₂O₂-stimulated cells. There was no significant difference in phospho-Akt (Ser 473 or Thr 308) expression among the groups.

CONCLUSIONS: Propofol 50 µM can reduce H₂O₂-induced damage and apoptosis in endothelial cells, by suppressing caspase-3 activity and by increasing eNOS expression via an Akt-independent mechanism.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999