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Blood, 15 July 2008, Vol. 112, No. 2, pp. 398-405. Prepublished online as a Blood First Edition Paper on May 13, 2008; DOI 10.1182/blood-2007-12-126714. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-12-126714v1 112/2/398    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Frei, A. C. Articles by Wandersee, N. J. Search for Related Content PubMed PubMed Citation Articles by Frei, A. C. Articles by Wandersee, N. J. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Vascular dysfunction in a murine model of severe hemolysis Anne C. Frei1, YiHe Guo1,2, Deron W. Jones3, Kirkwood A. Pritchard, Jr3, Karen A. Fagan4,5, Neil Hogg6, and Nancy J. Wandersee1,2 1 Blood Research Institute, Blood Center of Wisconsin, Milwaukee; 2 Department of Pediatrics and Children's Research Institute, Medical College of Wisconsin, Milwaukee; 3 Department of Pediatric Surgery, Medical College of Wisconsin, Milwaukee; 4 Department of Medicine, University of Colorado Health Sciences Center, Denver; 5 Division of Pulmonary and Critical Care Medicine and Center for Lung Biology, University of South Alabama, Mobile; and 6 Department of Biophysics, Medical College of Wisconsin, Milwaukee Spectrin is the backbone of the erythroid cytoskeleton; sph/sph mice have severe hereditary spherocytosis (HS) because of a mutation in the murine erythroid -spectrin gene. sph/sph mice have a high incidence of thrombosis and infarction in multiple tissues, suggesting significant vascular dysfunction. In the current study, we provide evidence for both pulmonary and systemic vascular dysfunction in sph/sph mice. We found increased levels of soluble cell adhesion molecules in sph/sph mice, suggesting activation of the vascular endothelium. We hypothesized that plasma hemoglobin released by intravascular hemolysis initiates endothelial injury through nitric oxide (NO) scavenging and oxidative damage. Likewise, electron paramagnetic resonance spectroscopy showed that plasma hemoglobin is much greater in sph/sph mice. Moreover, plasma from sph/sph mice had significantly higher oxidative potential. Finally, xanthine oxidase, a potent superoxide generator, is decreased in subpopulations of liver hepatocytes and increased on liver endothelium in sph/sph mice. These results indicate that vasoregulation is abnormal, and NO-based vasoregulatory mechanisms particularly impaired, in sph/sph mice. Together, these data indicate that sph/sph mice with severe HS have increased plasma hemoglobin and NO scavenging capacity, likely contributing to aberrant vasoregulation and initiating oxidative damage. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. J. Woollard, S. Sturgeon, J. P. F. Chin-Dusting, H. H. Salem, and S. P. Jackson Erythrocyte Hemolysis and Hemoglobin Oxidation Promote Ferric Chloride-induced Vascular Injury J. Biol. Chem., May 8, 2009; 284(19): 13110 - 13118. [Abstract] [Full Text] [PDF]

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