Alshaiban Abdulelah, Muralidharan-Chari Vandhana, Nepo Anne, Mousa Shaker A
The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA.
Pediatric Hematology/Oncology, Albany Medical College, Albany, NY, USA.
Clin Appl Thromb Hemost. 2016 Apr;22(3):230-8. doi: 10.1177/1076029614565880. Epub 2015 Jan 19.
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.
异常细胞黏附是镰状细胞病（SCD）血管闭塞性危机的主要原因之一。细胞间黏附分子1（ICAM-1）和P-选择素水平上调，导致白细胞和镰状红细胞（RBCs）与内皮细胞的黏附增加。本研究比较了硫酸化非抗凝肝素（S-NACH）衍生物与低分子量肝素替扎肝素对镰状RBCs与内皮细胞黏附的抑制作用。S-NACH对止血和出血的影响最小，并通过P-选择素干扰胰腺癌细胞与内皮细胞的结合。我们通过静态结合试验表明，用S-NACH预处理红细胞和内皮细胞均能显著抑制镰状RBCs与内皮细胞黏附的增加。S-NACH治疗还降低了SCD小鼠血浆中（黏附生物标志物）ICAM-1和P-选择素的较高水平。这项研究表明，有必要进一步研究S-NACH在治疗SCD患者血管闭塞且出血事件最少方面的潜在用途。
