Endothelial dysfunction and inflammatory process in transfusion-dependent patients with beta-thalassemia major

Aggeli, C.; Antoniades, Charalambos; Cosma, Constadina; Chrysohoou, Christine; Tousoulis, Dimitris; Ladis, Vassilios; Karageorga, M.; Pitsavos, Christos; Stefanadis, Christodoulos

doi:10.1016/j.ijcard.2004.12.025

Cited by 71 publications

(55 citation statements)

References 19 publications

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“…Iron-loading has been linked with endothelial function, circulating cholesterol oxidation products, and possibly coronary artery disease, whereas a procoagulant milieu in thalassemia may participate in accelerated atherogenesis [64][65][66]. In addition, activated leucocytes circulate in the peripheral blood in β-TM patients; and enhanced apoptosis, which is considered to participate in carotid plaque pathology [67,68].…”

Section: Discussionmentioning

confidence: 99%

“…Human serum albumin (HSA) is composed of 585 amino acids (66,438 Da), containing 17 pairs of intra-molecular disulfide bridges and one free cysteine (Cys34) [9]. HSA has the unique capability of binding reversibly or covalently to a wide diversity of ligands including water, cations (such as Ca 2+ , Na + and K + ), fatty acids, hormones, bilirubin and drugs [10].…”

Section: Introductionmentioning

confidence: 99%

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Ischemia-modified albumin as a marker of vascular dysfunction and subclinical atherosclerosis in β-thalassemia major

et al. 2017

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Background: Ischemia-modified albumin (IMA) is an altered type of serum albumin that forms under conditions of oxidative stress and an independent predictor of major adverse cardiovascular events. Objectives: To measure the levels of IMA in 45 children and adolescents with β-thalassemia major (β-TM) compared with 30 healthy controls and assess its relation to lipid peroxidation, vascular complications and subclinical atherosclerosis. Methods: β-TM patients without symptoms of heart disease were studied focusing on transfusion history, chelation therapy, serum ferritin, malondialdehyde (MDA) and IMA levels. Echocardiography was performed and carotid intima media thickness (CIMT) was assessed. Results: IMA and MDA levels were significantly higher in β-TM patients compared with controls (p < 0.001). IMA was higher among patients with heart disease, pulmonary hypertension risk and serum ferritin ≥2500 µg/l than those without. TM patients compliant to chelation had significantly lower IMA levels. IMA levels were positively correlated to MDA and CIMT while negatively correlated to ejection fraction and fractional shortening. Conclusion: Our results highlight the role of oxidative stress in the pathophysiology of vascular complications in thalassemia. IMA could be useful for screening of β-TM patients at risk of cardiopulmonary complications and atherosclerosis because its alteration occurs in early subclinical disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ischemia-modified albumin as a marker of vascular dysfunction and subclinical atherosclerosis in β-thalassemia major

et al. 2017

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“…40,41 Increased markers of endothelial damage in sph/sph mice The presence of increased levels of soluble VCAM-1 (sVCAM-1), E-selectin (sE-sel), and P-selectin (sP-sel) in plasma is indicative of increased vascular injury. 26,27,42 As shown in Figure 3A, levels of sVCAM-1 in the plasma of sph/sph mice were approximately 3.5-fold higher than those in the plasma of normal (ϩ/ϩ, sph/ϩ) mice (P Ͻ .0001). Similarly elevated plasma levels of sP-sel were found in sph/sph compared with normal (ϩ/ϩ, sph/ϩ) mice ( Figure 3C; P Ͻ .0001).…”

mentioning

confidence: 89%

Vascular dysfunction in a murine model of severe hemolysis

Frei

Guo

Jones

et al. 2008

Blood

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Spectrin is the backbone of the erythroid cytoskeleton; sph/sph mice have severe hereditary spherocytosis (HS) because of a mutation in the murine erythroid ␣-spectrin gene. sph/sph mice have a high incidence of thrombosis and infarction in multiple tissues, suggesting significant vascular dysfunction. In the current study, we provide evidence for both pulmonary and systemic vascular dysfunction in sph/sph mice. We found increased levels of soluble cell adhesion molecules in sph/ sph mice, suggesting activation of the vascular endothelium. We hypothesized that plasma hemoglobin released by intravascular hemolysis initiates endothelial injury through nitric oxide (NO) scavenging and oxidative damage. Likewise, electron paramagnetic resonance spectroscopy showed that plasma hemoglobin is much greater in sph/sph mice. Moreover, plasma from sph/sph mice had significantly higher oxidative potential. Finally, xanthine oxidase, a potent superoxide generator, is decreased in subpopulations of liver hepatocytes and increased on liver endothelium in sph/sph mice. These results indicate that vasoregulation is abnormal, and NO-based vasoregulatory mechanisms particularly impaired, in sph/sph mice. Together, these data indicate that sph/sph mice with severe HS have increased plasma hemoglobin and NO scavenging capacity, likely contributing to aberrant vasoregulation and initiating oxidative damage. (Blood. 2008;112:398-405) IntroductionThe membrane skeleton, a multiprotein complex located just beneath the plasma membrane, provides the red blood cells (RBCs) with the mechanical strength and deformability required to withstand the high shear forces of the microcapillaries. Spectrin, a tetramer composed of ␣-and ␤-subunits, is the backbone of the erythroid membrane skeleton and is tethered to the membrane at 2 positions. Disruption of either spectrin or proteins involved in tethering spectrin to the RBC plasma membrane can result in the hemolytic anemia known as hereditary spherocytosis (HS) in both humans and mice. [1][2][3] We have shown that sph/sph mice have severe autosomal recessive HS because of a spontaneous single-base deletion in the murine erythroid ␣-spectrin gene, Spna1. 4 Although heterozygous (sph/ϩ) mice are phenotypically normal, the sph/sph RBC is extremely fragile, resulting in an RBC life span of approximately 1 day (normal is 48 days). 5 As a consequence, sph/sph mice have a very severe hemolytic anemia, with hematocrit values of 0.15 to 0.20 and compensatory reticulocytosis of 90% to 95%. 5 As a result of the severe hemolysis, sph/sph mice with severe HS develop multiorgan pathology in kidney, heart, liver, and spleen. 6,7 In addition, sph/sph mice develop thrombosis and infarction in multiple tissues, 6-8 suggesting significant vascular dysfunction.Recent studies of patients with hemolytic anemia have indicated that the incidence of pulmonary hypertension, as indicated by increased tricuspid regurgitant jet velocity (Ն 3.0 m/sec), is relatively high in patients with sickle cell disease (SCD), thalassemia,...

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“…27,32 Platelets are also activated with enhanced aggregation, while splenectomy increases platelet counts and induces membranes abnormalities that further increase platelet aggregation. 32 The observed deficiency of the coagulation inhibitors, protein C and protein S, the elevated levels of thrombin-ATIII complex due to splenectomy and/or liver dysfunction as well as the co-inheritance of several coagulation defects, such as factor V (Leiden) and factor deficiency, may all contribute to the pathogenesis of hypercoagulability in thalassemia. 30,33 Finally, a strong inflammatory reaction has been observed.…”

Section: Hypercoagulabilitymentioning

confidence: 99%

Heart disease in thalassemia intermedia: a review of the underlying pathophysiology

Aessopos

Kati²,

Farmakis³

2007

Haematologica

100

110

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Endothelial dysfunction and inflammatory process in transfusion-dependent patients with beta-thalassemia major

Cited by 71 publications

References 19 publications

Ischemia-modified albumin as a marker of vascular dysfunction and subclinical atherosclerosis in β-thalassemia major

Ischemia-modified albumin as a marker of vascular dysfunction and subclinical atherosclerosis in β-thalassemia major

Vascular dysfunction in a murine model of severe hemolysis

Heart disease in thalassemia intermedia: a review of the underlying pathophysiology

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