title: The importance of the effect of shear stress on endothelial cells in determining the performance of hemoglobin based oxygen carriers.
abstract: The lack of blood donations and the threat of infections from blood and blood products have led to extensive research into the development of blood substitutes. The latest generation of hemoglobin based oxygen carriers (HBOC) has been shown to induce side effects like hypertension, vasoconstriction, inflammation and oxidative stress. HBOC are able to restore volemia and transport oxygen after a hemorrhagic shock, the reperfusion leading to the restoration of the blood flow in vessels. We propose an innovative approach, more closely emulating clinical situations, to assess the impact of HBOC perfusion on endothelial cells (EC) in vitro. Through this approach we quantified levels of oxidative stress, vasoactive factors and inflammation. EC were cultivated under a laminar flow to reproduce the return of shear stress (SS) during the reperfusion. We showed that heme oxygenase I transcription correlated with changes in oxidatively modified heme and methemoglobin; all were lower under SS. SS induced increased nitric oxide production, which may have implications for the mechanism of in vivo vasoconstriction and hypertension. E-selectin changes under SS were greater than those of ICAM-1. Our results demonstrate how it is essential to include SS in assays attempting to understand the potential vascular side effects of HBOC perfusion.
authors.affiliation: Groupe Ingénierie Cellulaire et Tissulaire, LEMTA-UMR 7563 IFR 111, Faculté de médecine, Avenue de la Forêt de Haye, Vandoeuvre-lès-Nancy, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Gaucher-Di Stasio
authors.forename: Estelle
authors.initials: E
authors.lastname: Paternotte
authors.forename: Christine
authors.initials: C
authors.lastname: Prin-Mathieu
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Reeder
authors.forename: Gaël
authors.initials: G
authors.lastname: Poitevin
authors.forename: Pierre
authors.initials: P
authors.lastname: Labrude
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Stoltz
authors.forename: Chris E
authors.initials: CE
authors.lastname: Cooper
authors.forename: Patrick
authors.initials: P
authors.lastname: Menu
mesh_terms: D001802:Blood Substitutes / Q000592:standards*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000201:enzymology / Q000378:metabolism*; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008706:Methemoglobin / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019087:Selectins / Q000235:genetics / Q000378:metabolism; D013314:Stress, Mechanical; D014662:Vasoconstrictor Agents / Q000378:metabolism
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D012333:RNA, Messenger; D019087:Selectins; D014662:Vasoconstrictor Agents; D018799:Intercellular Adhesion Molecule-1; D008706:Methemoglobin; D051547:Heme Oxygenase-1; D010100:Oxygen