Effect of Heparin Derivatives Versus P-Selectin Inhibitor on the Cellular Adhesion: A Potential Approach in the Management of Sickle Cell Disease
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Issue Date
2013
Authors
Alshaiban, Abdulelah Nasser '13
Degree
MS in Biotechnology
Advisor
Mousa, Shaker
Nepo, Anne G.
Nepo, Anne G.
Committee Members
MChari, Vandhana
Thangirala, Sudha
Thangirala, Sudha
Journal Title
Journal ISSN
Volume Title
Abstract
Abnormal cellular adhesion is one of the primary initiating factors in the development of sickle cell disease (SCD) complications, especially acute vaso-occlusive crisis. Both intercellular adhesion molecule-1 (ICAM-1) and P-selectin play important roles in leukocytes and sickle red blood cells (RBCs) adhesion to endothelium and get increased in response to different stimuli including inflammation in SCD. The potential effects of novel treatments, including non-anticoagulant heparin (NACH) and P-selectin inhibitor (PSI), on the process of sickle erythrocyte-endothelium adhesion were assessed in this study. Using PKH67 labeled RBCs, Static adhesion assays were conducted on human umbilical vein endothelial cells (HUVECs) and showed significant higher adhesion of sickle RBCs compared to normal RBCs. Pretreatment of both erythrocytes and endothelium with PSI or NACH showed a statistically significant inhibitory effect on sickle RBCs adhesion. Measurement of the adhesion biomarkers ICAM-1 and P-selectin showed significantly higher levels in the plasma of sickle mice compared to wild mice. Treatment studies of sickle mice with low-molecular weight heparin (LMWH) or NACH showed a decrease in ICAM-1 and P-selectin levels over time of treatment, with higher inhibitory effect by NACH. PSI treatment of sickle mice showed a decrease in P-selectin levels over time of treatment with no effect on ICAM-1 levels. Our results demonstrate the potential benefits of LMWH, NACH, and PSI in inhibiting the abnormal adhesion in SCD and signal further research to examine the effects of these compounds on other aspects of SCD pathogenesis.
Citation
Alshaiban, Abdulelah Nasser. "Effect of Heparin Derivatives Versus P-Selectin Inhibitor on the Cellular Adhesion : A Potential Approach in the Management of Sickle Cell Disease." Albany College of Pharmacy and Health Sciences, New York, Proquest/UMI, 2013.
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