The Endothelial Biology of Sickle Cell Disease: Inflammation and a Chronic Vasculopathy

Hebbel, Robert P.; Osarogiagbon, Raymond U.; Kaul, Dhananjay K.

doi:10.1080/10739680490278402

Cited by 239 publications

(179 citation statements)

References 213 publications

(345 reference statements)

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“…However, increased RBC adhesion to endothelial cells has been observed in various clinical states such as sickle cell disease, ␤-thalassemia, and diabetes mellitus, and the degree of RBC-EC adhesiveness has been linked to the vascular complications associated with these diseases (1)(2)(3)(4)(5). There is now general agreement that various cell surface alterations control the increased RBC adhesiveness in such disease states.…”

mentioning

confidence: 99%

Specific Binding of Red Blood Cells to Endothelial Cells Is Regulated by Nonadsorbing Macromolecules

Yang

Koo

Lin

et al. 2010

Journal of Biological Chemistry

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Abnormal adhesion of red blood cells to the endothelium has been linked to the pathophysiology of several diseases associated with vascular disorders. Various biochemical changes, including phosphatidylserine exposure on the outer membrane of red blood cells as well as plasma protein levels, have been identified as being likely to play a key role, but the detailed interplay between plasma factors and cellular factors remains unknown. It has been proposed that the adhesionpromoting effect of plasma proteins originates from ligand interaction, but evidence substantiating this assumption is often missing. In this work, we identified an alternative pathway by demonstrating that nonadsorbing macromolecules can also have a marked impact on the adhesion efficiency of red blood cells with enhanced phosphatidylserine exposure to endothelial cells. It is concluded that this adhesion-promoting effect originates from macromolecular depletion interaction and thereby presents an alternative mechanism by which plasma proteins could regulate cell-cell interactions. These findings should thus be of potential value for a detailed understanding of the pathophysiology of diseases associated with vascular complications and might be applicable to a wide range of cellcell interactions in plasma or plasma-like media. The adhesion of red blood cells (RBC)2 to endothelial cells (EC) is usually insignificant. However, increased RBC adhesion to endothelial cells has been observed in various clinical states such as sickle cell disease, ␤-thalassemia, and diabetes mellitus, and the degree of RBC-EC adhesiveness has been linked to the vascular complications associated with these diseases (1-5). There is now general agreement that various cell surface alterations control the increased RBC adhesiveness in such disease states. For example, an enhanced phosphatidylserine (PS) exposure on the outer leaflet of the RBC membrane has been linked to abnormal RBC-EC adhesion in sickle cell disease, hereditary hydrocytosis, and chronic uremia (6 -8). Usually this anionic phospholipid is located exclusively on the inner leaflet of the RBC membrane but is translocated to the outer leaflet in hemoglobinopathies and oxidative stress states (9). The role of PS in adhesion has not been fully understood, but RBC with enhanced PS exposure have been identified to establish specific interactions with EC or the endothelial matrix via several receptors including thrombospondin, ␣ V ␤ 3 , CD36, and PS receptor (6, 10, 11).Moreover, several plasma factors have been identified to be involved in abnormal RBC adhesion to EC. For example, fibrinogen enhances the adhesion of pathological RBC to EC (12, 13), which is consistent with the observation that the onset of vaso-occlusive crisis in sickle cell disease is always accompanied by a temporally elevated level of this acute phase protein (12,14). However, the underlying mechanisms behind the increased adhesion efficiency in the presence of this acute phase protein remain obscure. It has been suggested that fibrinogen acts...

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confidence: 99%

Specific Binding of Red Blood Cells to Endothelial Cells Is Regulated by Nonadsorbing Macromolecules

Yang

Koo

Lin

et al. 2010

Journal of Biological Chemistry

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“…On a global scale, a quarter of a million babies are diagnosed with this illness every year. The pathophysiology of this disease is due to a point mutation in hemoglobin that gives rise to sickling of erythrocytes resulting from the polymerization of hemoglobin S. Sickling plays a significant role in promoting vasoocclusive events that lead to ischemia-induced inflammation and pain (2,3). Sickle cell patients who have had surgery describe the pain associated with their disease as more severe than postoperative pain.…”

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confidence: 99%

Naloxone acts as a potent analgesic in transgenic mouse models of sickle cell anemia

Lunzer

Yekkirala

Hebbel

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…SCD is a constellation of disorders with either homozygous state (sickle-cell anemia) or Hb S in combination with another abnormal allele such as C (lysine replaces glutamic acid) or beta thalassemia trait (deletion or reduced expression of the beta allele) [1]. The central phenomenon is the paracrystal formation of affected hemoglobin in the deoxygenated state, resulting in microvascular obstruction, ischemia and tissue infarction.…”

Section: Introductionmentioning

confidence: 99%

Sickle-Cell Disease in Nigerian Children: Parental Knowledge and Laboratory Results

Obaro

Daniel

Lawson

et al. 2016

Public Health Genomics

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Background: Sickle-cell disease (SCD) is the most common inherited genetic disorder in sub-Saharan Africa, and it is associated with early mortality and lifelong morbidity. Early diagnosis is essential for instituting appropriate care and preventive therapy. Objective: To compare parental knowledge or perception of their offspring's hemoglobin phenotype prior to testing and actual validated laboratory test results. Methods: In a prospective community-based survey, we assessed parental knowledge of their children's hemoglobin phenotype and corroborated this with the results from a laboratory confirmatory test determined by high-performance liquid chromatography. Results: We screened 10,126 children aged less than 5 years. A total of 163 (1.6%) parents indicated that their offspring had been previously tested and had knowledge of the child's hemoglobin genotype. However, 51 (31.2%) of 163 parents of children who had been previously tested did not know the result of their offspring's test, and 18 (35.3%) of these 51 children were found to have SCD. Of those who claimed previous knowledge, 25 (15.3%) of 163 reported incorrect results. Overall, we identified 272 (2.76%) new cases from 9,963 children who had not been previously tested. Conclusion: There is the need to promote public awareness about SCD and the benefit of early diagnosis, quality assurance in laboratory diagnosis and institution of sustainable patient care pathways.

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The Endothelial Biology of Sickle Cell Disease: Inflammation and a Chronic Vasculopathy

Cited by 239 publications

References 213 publications

Specific Binding of Red Blood Cells to Endothelial Cells Is Regulated by Nonadsorbing Macromolecules

Specific Binding of Red Blood Cells to Endothelial Cells Is Regulated by Nonadsorbing Macromolecules

Naloxone acts as a potent analgesic in transgenic mouse models of sickle cell anemia

Sickle-Cell Disease in Nigerian Children: Parental Knowledge and Laboratory Results

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