scholarly journals Serum lipids and oxidized low density lipoprotein levels in sickle cell disease: Assessment and pathobiological significance

2014 ◽  
Vol 8 (2) ◽  
pp. 39-42 ◽  
Author(s):  
Alassane Diatta ◽  
Fatou Ciss ◽  
Tall Fatou Guye ◽  
Fatou Diallo ◽  
Fall Awa Oumar Tour ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Serum Lipids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Disease Assessment ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Cell Disease

Increased Circulating Soluble Lectin-Like Oxidized Low-Density Lipoprotein Receptor (sLOX-1) and Increased Endothelial Cell Expression of LOX-1 in Sickle Cell Disease (SCD): A Novel Marker for SCD Vasculopathy?

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 246-246
Author(s):  
Mingyi Chen ◽  
Xin Lin ◽  
Hannah Archibald ◽  
Ted Wun ◽  
Ralph Green
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Adhesion Molecules ◽  
Sickle Cell ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Density Lipoprotein Receptor ◽  
Enhanced Expression

Abstract Abstract 246 Introduction: Inflammation and abnormal adhesion of sickle red blood cells (RBCs), leukocytes and platelets to the vascular endothelium are postulated to play a central role in the pathogenesis of vaculopathy associated with sickle cell disease (SCD). Dysfunctional endothelial cells in the SCD vaso-occlusive process display vasoconstriction, proinflammatory and prothrombotic changes. Sickle RBCs may damage or activate the endothelium via enhanced expression of cell surface adhesion molecules such as vascular cell adhesion molecule (VCAM), intercellular adhesion molecules (ICAM), platelet endothelial cellular adhesion marker (PECAM), E- selectin, and P-selectin. In addition, SCD modulates high levels of circulating soluble adhesion molecules especially during the sickle cell crisis. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is an endothelial cell receptor for oxidized low-density lipoprotein. The enhanced expression of LOX-1 in endothelial cells has been identified in a variety of pathologic conditions including atherosclerosis, diabetic vasculopathy, hyperlipidemia and inflammation. The purpose of this study is to investigate changes in the expression of LOX-1 and its potential role in the pathogenesis of SCD vasculopathy. Methods: Using real time quantitative PCR, we analyzed LOX-1 gene expression in cultured human coronary endothelial cells (HCEC) following static incubation with sickle RBCs. We also measured circulating soluble LOX-1 (sLOX-1) concentrations by sandwich ELISA assay in SCD patient plasma. The statistical analysis was performed using Student's t-test. Results: LOX-1 gene expression in HCEC was significantly increased by incubation with sickle RBCs compared with normal RBCs. Upregulation was detected after 1 hour of incubation, and reached a peak after 6 hours. We studied 48 SCD (hemoglobin SS) patients (26 female, 22 male); vs 17 healthy (hemoglobin AA) control subjects (12 female, 5 male). The SCD cohort comprised pediatric and adult patients in steady-state (33 patients) and vaso-occlusive crisis (VOC; 15 patients). The concentration of circulating sLOX-1 protein in plasma of SCD patients (mean: 3.05±2.53 ng/mL; range 0.30 – 11.30 ng/mL) was significantly higher (p=0.0046) than in control healthy subjects (mean: 1.27±0.81 ng/mL). In the 15 SCD patients with VOC, sLOX-1 concentrations were higher, (mean: 3.65±2.40 ng/mL). Conclusions: Our study reveals that LOX-1 gene expression in endothelial cells is upregulated by incubation with SCD erythrocytes. Baseline circulating sLOX-1 levels are elevated in SCD patients compared with healthy controls. sLOX-1 levels are further elevated in VOC. Enhanced LOX-1 expression in endothelial cells may play a role in the pathophysiology of SCD vasculopathy. Studies of sLOX-1 in SCD may provide new insights into risk stratification, and may lead to novel therapeutic strategies for sickle cell patients with acute vascular complications. Disclosures: Green: Emisphere - Consultancy: Consultancy; Teva Pharmaceuticals - expert testimony: Consultancy.

Electron Paramagnetic Resonance Study of Cell-Free Hemoglobin in Sickle Cell Disease: Potential Antioxidant Role of Haptoglobin.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2345-2345
Author(s):  
Barbora Piknova ◽  
Mark T. Gladwin ◽  
Cheryl A. Hillery ◽  
Neil Hogg
Keyword(s):  
Sickle Cell Disease ◽  
Endothelial Function ◽  
Serum Albumin ◽  
Lipid Oxidation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Cell Disease ◽  
Free Hemoglobin ◽  
Epr Spectrum

Abstract It has previously been shown that red blood cell-free oxyhemoglobin (oxyHb) can affect endothelial function in Sickle Cell Disease (SCD) by virtue of its NO scavenging properties (Reiter et al, Nat Med, 2002). This reaction may have down-stream consequence via formation of metHb which has been demonstrated to have pro-oxidant properties and can oxidize low-density lipoprotein in vitro. In this study we have examined the fate of metHb in SCD vs normal plasma by examining the characteristic single line EPR signature of metHb in the g = 6 region. We show that the EPR signature of metHb differs in SCD compared with normals and exhibits a split EPR line indicative of a more rhombic heme geometry (See Figure). Figure Figure Addition of purified metHb to SCD plasma results in a conversion of the single line EPR spectrum to the rhombic form. By addition of hemin and hemoglobin to plasma constituents we have determined that the rhombic EPR spectrum is consistent with heme bound to serum albumin. In addition, immunoprecipitation of serum albumin from SCD plasma with EPR analysis of the IP fraction revealed the presence of albumin associated metHb. Interestingly, the transfer of heme from metHb to albumin is accelereated by the presence of low-density lipoprotein and inhibited by the addition of haptoglobin suggesting that plasma components can modulate heme release from metHb and that the lack of haptoglobin in SCD plasma allowed the transfer of heme from metHb to albumin. To confirm this we added metHb to SCD plasma in the presence and absence of haptoglobin and observed that the addition of haptoglobin prevented conversion of the metHb spectrum to the albumin associated split (rhombic) species. From these studies we conclude that plasma haptoglobin not only binds hemoglobin but also limits heme release from metHb. To examine potential oxidative consequences of this effect, we incubated LDL with metHb in the presence and absence of haptoglobin. Haptoglobin inhibited LDL oxidation in a dose-dependent manner. Interestingly, the 1-1 isoform of haptoglobin was much more effective than the 2-2 isoform, in agreement with published studies on the efficacy of hemoglobin binding to the two haptoglobin varieties. Additionally, we have measured levels of 8-isoprostanes in the plasma of SCD patients as an index of lipid oxidation and show that 8-isoprostane levels are significantly elevated in SCD patients (295 209 pg/ml, mean S.D., n= 13, vs. 69 37 pg/ml, mean S.D. n= 5 for normal controls). In conclusion, these studies provide evidence that the saturation of the haptoglobin clearance mechanisms in hemolytic disorders such as SCD can not only affect the NO-axis of endothelial function due to increases in cell-free hemoglobin, but can also lead to altered heme metabolism leading to lipid oxidation and formation of pro-inflammatory lipids which have the potential to alter both endothelial and red cell function.

Lipoprotein Cholesterol and Triglyceride in Children with Steady-State Sickle Cell Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1547-1547
Author(s):  
Magda Oliveira Seixas ◽  
Larissa Rocha ◽  
Mauricio Carvalho ◽  
Joelma Menezes ◽  
Isa Lyra ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Cell Disease ◽  
Low Density Lipoprotein Cholesterol

Abstract Abstract 1547 Poster Board I-570 Introduction Levels of high-density lipoprotein cholesterol have been correlated with anti-inflammatory, anti-oxidative, anti-aggregation, anti-coagulant and pro-fibrinolytic activities. We hypothesized that lipoprotein cholesterol and triglycerides have important roles in sickle cell disease pathogenesis. Patients and Methods A prospective study of biochemical and hematological analyses of 152 steady-state children with sickle cell disease and 132 healthy subjects using immunochemistry, immunoassay and electronic cell counter respectively. Clinical data were collected from patient medical records. Data analyses were performed using Prism 5.01 (Graphpad Software, San Diego, CA), EPIinfo 6.04 (CDC, Atlanta, Georgia) and STATA SE 10 software (StataCorp, Texas, USA). Results There was a significant positive association of high-density lipoprotein cholesterol with hemoglobin (p<0.001), hematocrit (p<0.001) and total cholesterol (p<0.001) and a negative association with reticulocytes (p=0.046), leukocytes (p=0.015), monocytes (p=0.004) and platelets (p=0.005), bilirubins [total bilirubin (p<0.001), direct bilirubin (p<0.001) and indirect bilirubin (p<0.001], iron (p<0.001), aminotransferases [aspartate aminotransferase (p=0.004), alanine aminotransferase (p=0.035)], lactate dehydrogenase (p<0.001), urea (p=0.030), alpha 1-antitrypsin (p<0.001), very low-density lipoprotein cholesterol (p=0.003), triglycerides (p=0.005) and hemoglobin S (p=0.002). Low high-density lipoprotein cholesterol concentration was associated with cardiac abnormalities (p<0.025), pneumonia history (p=0.033) and blood transfusion use (p=0.025). Triglycerides (p=0.047), very low-density lipoprotein cholesterol (p=0.044), low-density lipoprotein cholesterol (p=0.033), total cholesterol (p=0.007), alpha 1-antitrypsin (p=0.040) and ferritin (p=0.008) levels were associated with cholelithiasis. Conclusion We hypothesize that some SCD patients can have a specific dyslipidemic subphenotype characterized by hypertriglyceridemia, high VLDL-C and low plasma LDL-C and HDL-C in association with other biomarkers, including those related to inflammation. This represents an important step toward a more reliable clinical prognosis. We suggest further studies and continued research into new mechanisms involving this complex network of markers in order to establish their role in SCD pathogenesis. Disclosures No relevant conflicts of interest to declare.

scholarly journals The effects of long-term moderate exercise and Western-type diet on oxidative/nitrosative stress, serum lipids and cytokines in female Sprague Dawley rats

2021 ◽  
Author(s):  
Maria Donatella Semeraro ◽  
Gunter Almer ◽  
Melanie Kaiser ◽  
Sieglinde Zelzer ◽  
Andreas Meinitzer ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Serum Lipids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Low Density Lipoprotein Cholesterol ◽  
High Fat ◽  
Nitric Oxide Metabolites

Abstract Purpose Regular exercise reduces obesity and the risk of cardiovascular disease. However, health-promoting benefits of physical activity are commonly associated with increased inflammation and oxidative stress. Here, we tested whether constant moderate exercise is able to prevent or attenuate the oxidative/nitrosative stress, inflammation, and serum lipids in lean and obese rats. Methods Four-month-old female Sprague Dawley rats received standard or a high-fat diet. Animals were subjected to a physical activity protocol, consisting of 30 min forced treadmill exercise for 5 consecutive days per week during 10 months. Baseline and sedentary (non-exercised) rats were used as controls. Lipids, oxidized low-density lipoprotein cholesterol, nitric oxide metabolites, and pro- and anti-inflammatory markers were measured in blood collected upon euthanasia. Results At variance to young baseline control rats, 14-month-old animals fed normal diet had increased plasma lipid levels, including total cholesterol and triglycerides, which were further elevated in rats that consumed a high-fat diet. While treadmill exercise did not lower the amount of serum lipids in standard diet group, forced physical activity reduced non-high-density lipoprotein cholesterol in response to high-fat diet feeding. Exercised rats fed standard diet or high-fat diet had lower abundancy of nitric oxide metabolites, which coincided with increased levels of oxidized low-density lipoprotein cholesterol. Accordingly, the amount of nitric oxide metabolites correlated inversely with oxidized low-density lipoprotein cholesterol and homo-arginine. Exercise significantly reduced inflammatory cytokines in high-fat diet fed rats only. Conclusion Our study suggests that regular exercise alters the equilibrium between oxidative and anti-oxidative compounds and reduces pro-inflammatory cytokines.

Efficacy of Atorvastatin Therapy in Ischaemic Heart Disease – Effects on Oxidized Low-density Lipoprotein and Adiponectin

2007 ◽  
Vol 35 (4) ◽  
pp. 534-539 ◽  
Author(s):  
K Miyagishima ◽  
S Hiramitsu ◽  
S Kato ◽  
Y Kato ◽  
F Kitagawa ◽  
...  
Keyword(s):  
Heart Disease ◽  
Ischaemic Heart Disease ◽  
Serum Lipids ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Atorvastatin Therapy

The lipid-lowering and anti-atherosclerotic effects of atorvastatin (10 mg/day) were investigated by measuring changes in the levels of oxidized low-density lipoprotein (LDL), serum lipids (total cholesterol [TC], LDL-cholesterol [LDL-C] and triglycerides [TG]), and in the protein adiponectin. This was undertaken in 22 patients with ischaemic heart disease and serum LDL-C levels > 100 mg/dl. After 3 months of therapy, atorvastatin significantly decreased serum lipids, oxidized LDL was reduced from 457.0 ± 148.6 to 286.9 ± 88.5 nmol/l, and adiponectin increased from 9.7 ± 7.4 to 13.9 ± 9.98 μg/ml. No significant correlation was observed between adiponectin and LDL-C, TG and high-density lipoprotein cholesterol. Atorvastatin therapy was not associated with side-effects, such as myalgia and gastrointestinal disorders, and did not give abnormal laboratory test results. It is concluded that atorvastatin decreases serum lipid and oxidized LDL levels, and increases adiponectin levels in patients with ischaemic heart disease.

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