title: Cellular adhesion and the endothelium: P-selectin.
abstract: P-selectin on endothelial cell surfaces is central to impaired microvascular blood flow in sickle cell disease (SCD). Restoration of blood flow is expected to provide therapeutic benefit for SCD patients, whatever the mechanism of action of the treatment. Long-term oral administration of a P-selectin-blocking agent potentially improves blood flow and averts acute painful vaso-occlusive crises in patients with SCD. This review focuses on the pathophysiology of the impairment of microvascular blood flow in SCD with an emphasis on the role of P-selectin and summarizes the status of development of antiselectin therapies as a means of improving microvascular flow.
authors.affiliation: Sickle Cell Center, Department of Medicine, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Kutlar
authors.affiliation: Department of Medicine, University of California San Francisco School of Medicine, 505 Parnassus Avenue, San Francisco, CA 94143, USA; Vanguard Therapeutics, Inc, 108 Eagle Trace Drive, Half Moon Bay, CA 94019-2286, USA. Electronic address: shembury@gmail.com.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Embury
mesh_terms: D000755:Anemia, Sickle Cell / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D006017:Glycolipids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006912:Hydroxyquinolines / Q000494:pharmacology / Q000627:therapeutic use; D019007:P-Selectin / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D006017:Glycolipids; D006912:Hydroxyquinolines; D019007:P-Selectin; D010426:Pentosan Sulfuric Polyester; C553182:rivipansel; C514191:2-(4-chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo(H)quinoline-4-carboxylic acid
keywords: Impaired blood flow in sickle cell disease; Microvascular occlusion; P-selectin; Pentosan polysulfate sodium; Sickle cell disease; Sickle red cell adhesion