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

2018 ◽  
Vol 7 (1) ◽  
pp. 1
Author(s):  
Charles Antwi-Boasiako ◽  
John Ahenkorah ◽  
Eric Donkor ◽  
Bartholomew Dzudzor ◽  
Gifty Dankwah ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sickle Cell Disease ◽  
Adhesion Molecules ◽  
Sickle Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Disease ◽  
Soluble Adhesion Molecules ◽  
Endothelial Adhesion Molecules ◽  
Nitric Oxide Metabolites ◽  
Study Participants

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.

scholarly journals Correlation of lipid peroxidation and nitric oxide metabolites, trace elements, and antioxidant enzymes in patients with sickle cell disease

2020 ◽  
Vol 34 (7) ◽  
Author(s):  
Charles Antwi‐Boasiako ◽  
Gifty Boatemaah Dankwah ◽  
Robert Aryee ◽  
Charles Hayfron‐Benjamin ◽  
George Aboagye ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lipid Peroxidation ◽  
Trace Elements ◽  
Antioxidant Enzymes ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease ◽  
Nitric Oxide Metabolites

scholarly journals Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease

Blood ◽  
2006 ◽  
Vol 107 (6) ◽  
pp. 2279-2285 ◽  
Author(s):  
Gregory J. Kato ◽  
Vicki McGowan ◽  
Roberto F. Machado ◽  
Jane A. Little ◽  
James Taylor ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Lactate Dehydrogenase ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Serum Lactate Dehydrogenase ◽  
Cell Disease ◽  
Intravascular Hemolysis ◽  
Soluble Adhesion Molecules ◽  
Risk Of Death

AbstractPulmonary hypertension is prevalent in adult patients with sickle cell disease and is strongly associated with early mortality and markers of hemolysis, in particular, serum lactate dehydrogenase (LDH). Intravascular hemolysis leads to impaired bioavailability of nitric oxide (NO), mediated by NO scavenging by plasma oxyhemoglobin and by arginine degradation by plasma arginase. We hypothesized that serum LDH may represent a convenient biomarker of intravascular hemolysis and NO bioavailability, characterizing a clinical subphenotype of hemolysis-associated vasculopathy. In a cohort of 213 patients with sickle cell disease, we found statistically significant associations of steady-state LDH with low levels of hemoglobin and haptoglobin and high levels of reticulocytes, bilirubin, plasma hemoglobin, aspartate aminotransferase, arginase, and soluble adhesion molecules. LDH isoenzyme fractionation confirmed predominance of LD1 and LD2, the principal isoforms within erythrocytes. In a subgroup, LDH levels closely correlated with plasma cell-free hemoglobin, accelerated NO consumption by plasma, and impaired vasodilatory responses to an NO donor. Remarkably, this simple biomarker was associated with a clinical subphenotype of pulmonary hypertension, leg ulceration, priapism, and risk of death in patients with sickle cell disease. We propose that LDH elevation identifies patients with a syndrome of hemolysis-associated NO resistance, endothelial dysfunction, and end-organ vasculopathy.

Lactate Dehydrogenase as a Biomarker of Hemolysis-Associated Nitric Oxide Resistance, Priapism, Leg Ulceration, Pulmonary Hypertension and Death in Patients with Sickle Cell Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3188-3188 ◽  
Author(s):  
Gregory J. Kato ◽  
Vicki McGowan ◽  
Roberto F. Machado ◽  
Jane A. Little ◽  
James Taylor ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Lactate Dehydrogenase ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Serum Lactate Dehydrogenase ◽  
Cell Disease ◽  
Intravascular Hemolysis ◽  
Soluble Adhesion Molecules ◽  
Risk Of Death

Abstract Pulmonary hypertension is prevalent in adult patients with sickle cell disease, and is strongly associated with markers of hemolysis, in particular serum lactate dehydrogenase (LDH), and early mortality. Intravascular hemolysis leads to a state of resistance to nitric oxide (NO), mediated by NO scavenging by plasma oxyhemoglobin and by arginine degradation by plasma arginase. We hypothesized that serum LDH may represent a convenient biomarker of intravascular hemolysis and NO bioavailability, characterizing a clinical subphenotype of hemolysis-associated vasculopathy. In a cohort of 213 patients with sickle cell disease, we found statistically significant associations of LDH with low levels of hemoglobin and haptoglobin and high levels of reticulocytes, bilirubin, plasma hemoglobin, aspartate aminotransferase, arginase and soluble adhesion molecules. LDH isoenzyme fractionation confirmed predominance of LD1 and LD2, the principal isoforms within erythrocytes. In a subgroup, LDH levels closely correlated with plasma cell free hemoglobin, accelerated nitric oxide consumption by plasma and impaired vasodilatory responses to an NO donor. Remarkably, this simple biomarker was statistically associated with a clinical subphenotype of pulmonary hypertension, leg ulceration, priapism, and risk of death in patients with sickle cell disease. We propose that LDH elevation identifies patients with a syndrome of hemolysis-associated NO-resistance, endothelial dysfunction and end-organ vasculopathy. Figure Figure Figure Figure

Effect of Short-Term Simvastatin Treatment on Endothelial Adhesion Molecules in Sickle Cell Disease: A Pilot Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1070-1070
Author(s):  
Carolyn Hoppe ◽  
Frans A Kuypers ◽  
Sandra K Larkin ◽  
Robert Hagar ◽  
Elliott Vichinsky ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Adhesion Molecules ◽  
Sickle Cell ◽  
Vascular Function ◽  
Cellular Adhesion ◽  
Lipid Lowering ◽  
Cell Disease ◽  
Short Term ◽  
Simvastatin Treatment ◽  
Endothelial Adhesion Molecules

Abstract Abstract 1070 Inflammation and abnormal adhesion of leukocytes and sickle red blood cells (RBC) to the vascular endothelium are postulated to play a central role in the pathogenesis of sickle cell disease (SCD). The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to improve vascular function, independent of their lipid-lowering properties, by restoring nitric oxide (NO) bioavailability and suppressing the inflammatory response to endothelial injury. We previously documented an increase in plasma NO (nitrate) levels, as well as a reduction in plasma IL-6 and hs-CRP levels in SCD patients treated with simvastatin. In this study, we investigated the effect of simvastatin treatment on levels of circulating endothelial adhesion molecules, including vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecules (ICAM-1, ICAM-3), platelet endothelial cellular adhesion marker (PECAM), E- selectin, P-selectin as well as vascular endothelial growth factor (VEGF) in SCD patients. Twenty-eight subjects with SCD were treated with 20mg (n=16) or 40mg (n=12) of simvastatin daily for 21 days using a dose-escalating approach. Short-term simvastatin treatment resulted in decreased levels of plasma VCAM-1 (−22%, p=0.003), ICAM-1 (−7%, p=0.004), ICAM-3 (−24%, p=0.01), E-selectin (−9%, p=0.01) and VEGF (−35%, p=0.002) from baseline. The relative change in biomarker levels did not differ between the 20mg and 40mg treatment groups. Among HbSS subjects, ICAM-3 (p=0.02) and P-selectin (p=0.007) decreased to a greater extent in subjects who were not receiving hydroxyurea (HU) therapy compared to subjects who were on HU therapy. Simvastatin holds promise as a potential new treatment for patients with SCD. Disclosures: Off Label Use: Zocor (simvastatin) use in sickle cell disease.

Role of Adhesion Molecules and Vascular Endothelium in the Pathogenesis of Sickle Cell Disease

Hematology ◽  
2007 ◽  
Vol 2007 (1) ◽  
pp. 84-90 ◽  
Author(s):  
Marilyn J. Telen
Keyword(s):  
Sickle Cell Disease ◽  
Red Blood Cells ◽  
Adhesion Molecules ◽  
Sickle Cell ◽  
Vascular Endothelium ◽  
Blood Cells ◽  
Cell Disease ◽  
Adhesive Interactions ◽  
Lines Of Evidence

AbstractA number of lines of evidence now support the hypothesis that vaso-occlusion and several of the sequelae of sickle cell disease (SCD) arise, at least in part, from adhesive interactions of sickle red blood cells, leukocytes, and the endothelium. Both experimental and genetic evidence provide support for the importance of these interactions. It is likely that future therapies for SCD might target one or more of these interactions.

scholarly journals Vitamin D and Nonskeletal Complications among Egyptian Sickle Cell Disease Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Mona Hamdy ◽  
Niveen Salama ◽  
Ghada Maher ◽  
Amira Elrefaee
Keyword(s):  
Vitamin D ◽  
Sickle Cell Disease ◽  
Vitamin D Deficiency ◽  
Sickle Cell ◽  
Standard Of Care ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Disease ◽  
P Values ◽  
Indirect Bilirubin ◽  
Deficient Group

Lower levels of vitamin D have been documented in many patients with sickle cell disease (SCD), but data are still inconclusive regarding the association between vitamin D deficiency (VDD) and the occurrence or the severity of various SCD complications. Our study aimed to detect the prevalence of vitamin D deficiency among Egyptian patients with SCD and to associate it with the clinical course of the disease. We measured the level of 25-hydroxy vitamin D in 140 children (age from 4.3 to 15.5years), 80 patients with SCD and 60 controls using enzyme-linked immunosorbent assay. Vitamin D was deficient in 60% of SCD compared to 26.7% of controls. Severe VDD was significantly higher in SCD patients than controls. Patients were divided into 2 groups; Normal group (32 patients) and Deficient group (48 patients). There were statistically significant differences between the 2 groups regarding their age, height percentile, the presence of clinical jaundice, and osseous changes (P values 0.043, 0.024, 0.001, and 0.015, respectively). Hemoglobin and hematocrit values were significantly lower in Deficient group (P values 0.022 and 0.004, respectively) while the levels of aspartate aminotransferase, lactate dehydrogenase, and total and indirect bilirubin were significantly higher in the same group (P values 0.006, 0.001, 0.038, and 0.016, respectively). The frequency of blood transfusions, hospitalization, and vasoocclusive crisis previous year as well as the history of bone fracture and recurrent infections proved to be significantly higher in Deficient group. These findings suggest that VDD may play a role in the pathogenesis of hemolysis and other complication of SCD. Vitamin D monitoring and supplementation in patients with SCD should be implemented as a standard of care to potentially improve health outcomes in these affected patients.

scholarly journals Increased adhesive properties of neutrophils in sickle cell disease may be reversed by pharmacological nitric oxide donation

Haematologica ◽  
2008 ◽  
Vol 93 (4) ◽  
pp. 605-609 ◽  
Author(s):  
A. A. Canalli ◽  
C. F. Franco-Penteado ◽  
S. T.O. Saad ◽  
N. Conran ◽  
F. F. Costa
Keyword(s):  
Nitric Oxide ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease ◽  
Adhesive Properties

The metabolites of nitric oxide in sickle-cell disease

1995 ◽  
Vol 91 (4) ◽  
pp. 834-837 ◽  
Author(s):  
David C. Rees ◽  
Paul Cervi ◽  
David Grimwade ◽  
Aisling O'Driscoll ◽  
Malcolm Hamilton ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease

Abstract P726: Cytochrome B5 Reductase 3 Modifies The Brain-Blood Axis Response To Ischemic Stroke In Mice With Sickle Cell Disease

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Katherine C Wood ◽  
Heidi M Schmidt ◽  
Scott Hahn ◽  
Mehdi Nouraie ◽  
Mara Carreno ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ischemic Stroke ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
African Ancestry ◽  
Cytochrome B5 ◽  
Heme Iron ◽  
Wild Type ◽  
Cell Disease ◽  
Cytochrome B5 Reductase

Introduction: Stroke and silent infarcts are serious complications of sickle cell disease (SCD), occurring frequently in children. Decreased nitric oxide bioavailability and responsiveness contribute to neurovascular disease. Cytochrome b5 reductase 3 (Cyb5R3) is a heme iron reductase that reduces oxidized soluble guanylate cyclase heme iron (Fe 3+ --> Fe 2+ ) to preserve nitric oxide signaling. A loss-of-function Cyb5R3 missense variant (T117S) occurs with high frequency (0.23 minor allele) in persons of African ancestry. Hypothesis: We hypothesized that impaired reductase function of T117S Cyb5R3 exacerbates brain damage after ischemic stroke in SCD. Methods: Bone marrow transplant was used to create male SCD mice with wild type (SS/WT) or T117S (SS/T117S) Cyb5R3. Blood was sampled before and after middle cerebral artery occlusion (55 minutes occlusion, 48 hours reperfusion). Infarct volume (IV) was determined by 2,3,5-triphenyltetrazolium chloride. Intravascular hemolysis and correlation (Pearson’s R) of hematology changes with IV were determined. Baseline Walk-PHaSST (NCT00492531) data were analyzed for stroke occurrence. Results: Brain IV (63 vs 27 cm 3 , P=0.003) and mortality (3/6 vs 0/8) were greater in SS/T117S vs SS/WT. Red blood cells, hemoglobin and hematocrit declined as IV increased. Plasma oxyhemoglobin increased in parallel with IV (r = 0.74, P=0.09). There were different signatures to hematologic changes that occurred with IV in SCD. Relative to wild type, T117S contracted the erythroid compartment (red blood cell: -13% vs 13%, P=0.003; hematocrit: -20% vs 1%, P=0.008; hemoglobin: -18% vs 2%, P=0.007). Mean platelet volume correlated with IV in SS/T117S (r = 0.87, P=0.06), while the inverse occurred in SS/WT (r = -0.63, P=0.09) Monocytes increased in parallel with IV in SS/T117S (r = 0.73, P=0.16), but followed the opposite trajectory in SS/WT (r = -0.77, P=0.04). WalkPHaSST participants with T117S Cyb5R3 self-reported more ischemic stroke (7.4% vs 5.1%) relative to wild type. Conclusion: Cyb5R3 is an important modifier of the evolution and outcome of ischemic brain injury in SCD and its hematologic consequences. Our findings indicate a bidirectional relationship between stroke and anemia in SCD that may axially turn on Cyb5R3 activity.

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