Correlation Between Soluble Endothelial Adhesion Molecules and Nitric Oxide Metabolites in Sickle Cell Disease.

Nitric Oxide (NO) and soluble adhesion molecules are promising biomarkers, which predict endothelial dysfunction in sickle cell disease (SCD). Several studies have investigated the relationship between NO (as well as its metabolites) and endothelial adhesion molecules in SCD. However, these studies were done mainly in the developed world, and it is difficult to extrapolate the findings to SCD populations in other geographical regions such as Africa due to significant disparities in the results. The aim of the current study was to determine the correlation between levels of nitric oxide metabolites (NOx) and adhesion molecules in SCD patients in a tertiary hospital in Ghana. A case control cross-sectional study involving 100 SCD (made up of HbSS and HbSC patients) and 60 healthy controls was conducted. Concentrations of NOx and soluble endothelial adhesion molecules (ICAM-1, VCAM-1 and E-selectin) were measured in all the study participants (n = 160) by the Griess reagent system and enzyme-linked immunosorbent assay (ELISA). Correlation analysis was performed to determine a possible link between the variables. Levels of soluble adhesion molecules were higher in the HbSS patients. Correlation of NOx with ICAM-1 almost approached significance (r = 0.565, p = 0.058) in the HbSS patients. There were no correlations between NOx and E-selectin in both HbSS and HbSC patients. There were no significant correlations between NOx and VCAM-1 in all the study participants (p > 0.05). Of the soluble adhesion molecules, ICAM-1 showed a significant positive correlation with VCAM-1 in the HbSC patients. There were no significant differences between the adhesion molecules and the age of participants in the various study groups. Whether or not a significant correlation exists between NOx and soluble adhesion molecules may not depend on the sickle cell genotype. The expression of adhesion molecules may not depend on age.

Levels of Soluble Endothelium Adhesion Molecules and Complications among Sickle Cell Disease Patients in Ghana.

BACKGROUND: Soluble adhesion molecules are involved in the gathering and joining of inflammatory cells to vascular endothelium. Therefore, they serve as potential markers of endothelial dysfunction in vascular diseases including sickle cell disease (SCD). In Ghana, there are scarcely any report on the levels of adhesion molecules among SCD patients. The current study aimed to determine plasma levels of ICAM-1, VCAM-1 and E-Selectin as markers of endothelial dysfunction in SCD patients in steady state, complications and controls. METHODOLOGY: This was a cross-sectional study involving 60 HbAA controls, 46 HbSS steady state, 57 HbSS VOC, 18 HbSC VOC, 21 HbSS with leg ulcer and 11 HbSS with priapism. Blood samples were collected from all the study subjects (n = 213) and processed into plasma. The plasma levels of VCAM-1, ICAM-1 and E-Selectin concentrations of SCD patients and controls were measured using a double sandwich ELISA technique. Demographic information was also collected from the study subjects. RESULTS: Levels of all soluble proteins (ICAM-1, VCAM-1 and E-Selectin) were significantly higher in HbSS steady-state patients compared to non-SCD controls (p < 0.001). Generally, SCD patients with complications had relatively higher levels of the soluble proteins compared to those in the steady-state. Of the SCD patients with complications, those with vaso-occlusion crisis (HbSS VOC) had relatively higher levels of ICAM-1, VCAM-1 and E-Selectin at (62.42 ng/mL ± 26.09), (634.99 ng/mL ± 324.31) and (236.77 ng/mL ± 114.40) respectively; Conclusion: Although levels of adhesion molecules were high in all the SCD patients with complications, those with vaso-occlusive crisis had higher levels. This might reflect an ongoing endothelial dysfunction in these patients. SCD patients with vaso-occlusive crisis presents with a more severe pathophysiology condition.

Elevated Proangiogenic Markers are Associated with Vascular Complications within Ghanaian Sickle Cell Disease Patients.

: Sickle cell disease (SCD) is an inherited blood disorder that can result in vasculopathy and end organ damage. Angiogenesis has been implicated as a key contributing factor to vascular mediated tissue injury in SCD. The relative plasma levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and vascular endothelial growth factor (VEGF) greatly influence angiogenesis. Dysregulation of these growth factors, leading to a pro-angiogenic state in SCD patients, has been documented in the developed world but there is very little data in Africa. There is the need, therefore, for studies in Ghanaian SCD patients. The aim of this study was to assess plasma levels of Ang-1, Ang-2, and VEGF in homozygous (HbSS) SCD patients with or without complications and healthy controls (HbAA) in Ghana. The study was a case-control study involving 544 participants: 396 HbSS SCD patients and 148 HbAA healthy controls. The study was conducted at the Center for Clinical Genetics (Sickle Cell Clinic) and Accra Area Blood Centre for National Blood transfusion at the Korle-Bu Teaching Hospital, Accra, Ghana. The plasma levels of Ang-1, Ang-2, and VEGF of study participants were measured with a double sandwich enzyme-linked immunosorbent assay (ELISA) technique. Complete blood count (CBC) was measured with an autoanalyser. The mean plasma Ang-1, Ang-2, and VEGF were significantly higher in HbSS SCD patients with or without complications than healthy controls (p < 0.001). The Ang-2/Ang-1 ratio was significantly lower in the controls than the HbSS patients (p < 0.001). The Ang-2/Ang-1 ratio was higher in the HbSS patients with leg ulcers as compared with patients with other complications and healthy controls (p < 0.001). There were higher leucocyte counts in HbSS patients than healthy controls. Overall, there was elevated plasma levels of Ang-1, Ang-2, and VEGF in SCD patients. The higher Ang-2/Ang-1 plasma levels in patients with leg ulcers suggests a possible ongoing angiogenesis and response to inflammatory stimuli. The study provides a first report on plasma levels of angiopoietin-1, angiopoietin-2, and vascular endothelial growth factors in homozygous sickle cell disease patients in Ghana.