title: Modulation of Sickle Red Blood Cell Adhesion and its Associated Changes in Biomarkers by Sulfated Nonanticoagulant Heparin Derivative.
abstract: Abnormal cellular adhesion is one of the primary causes of vaso-occlusive crisis in sickle cell disease (SCD). Levels of intercellular adhesion molecule 1 (ICAM-1) and P-selectin are upregulated, resulting in increased adhesion of leukocytes and sickle red blood cells (RBCs) to endothelium. This study compares the inhibitory effect of a sulfated nonanticoagulant heparin (S-NACH) derivative with a low-molecular-weight heparin, tinzaparin, on the adhesion of sickle RBCs to endothelium. The S-NACH exhibits minimum effects on hemostasis and bleeding and interferes with the binding of pancreatic cancer cells to endothelial cells via P-selectin. We show by static binding assay that pretreatment of both erythrocytes and endothelial cells with S-NACH significantly inhibits the increased adhesion of sickle RBCs to endothelial cells. The S-NACH treatment also decreases the higher plasma levels of (adhesion biomarkers) ICAM-1 and P-selectin in SCD mice. This investigation signals further research into the potential use of S-NACH in treating vaso-occlusions with minimal bleeding events in patients with SCD.
authors.affiliation: The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA.
authors.forename: Abdulelah
authors.initials: A
authors.lastname: Alshaiban
authors.affiliation: The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA.
authors.forename: Vandhana
authors.initials: V
authors.lastname: Muralidharan-Chari
authors.affiliation: Pediatric Hematology/Oncology, Albany Medical College, Albany, NY, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Nepo
authors.affiliation: The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA shaker.mousa@acphs.edu.
authors.forename: Shaker A
authors.initials: SA
authors.lastname: Mousa
mesh_terms: D000755:Anemia, Sickle Cell / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D004913:Erythrocytes, Abnormal / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D019007:P-Selectin / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C573420:ICAM1 protein, human; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1; D006493:Heparin
keywords: ICAM-1; adhesion molecules; endothelial cells; heparin; selectin; sickle cell disease; sickle red blood cells; sulfated nonanticoagulant heparin; tinzaparin