Elevated Circulating Angiogenic Progenitors and White Blood Cells Are Associated with Hypoxia-Inducible Angiogenic Growth Factors in Children with Sickle Cell Disease

We studied the number and function of angiogenic progenitor cells and growth factors in children aged 5–18 years without acute illness, 43 with Hemoglobin SS and 68 with normal hemoglobin. Hemoglobin SS subjects had at least twice as many mononuclear cell colonies and more circulating progenitor cell than Control subjects. Plasma concentrations of erythropoietin, angiopoietin-2, and stromal-derived growth factor (SDF)-1α were significantly higher in children with Hemoglobin SS compared to Control subjects. In a multivariate analysis model, SDF-1α concentration was found to be associated with both CPC number and total white blood cell count in the Hemoglobin SS group, suggesting that SDF-1α produced by ischemic tissues plays a role in mobilizing these cells in children with Hemoglobin SS. Despite having a higher number of angiogenic progenitor cells, children with Hemoglobin SS had slower migration of cultured mononuclear cells.

[1]  S. G. Betal,et al.  Increased levels of the inflammatory biomarker C-reactive protein at baseline are associated with childhood sickle cell vasocclusive crises , 2010, British journal of haematology.

[2]  M. Gladwin,et al.  Angiogenic and Inflammatory Markers of Cardiopulmonary Changes in Children and Adolescents with Sickle Cell Disease , 2009, PloS one.

[3]  Dean P. Jones,et al.  Measuring the poise of thiol/disulfide couples in vivo. , 2009, Free radical biology & medicine.

[4]  A. Duits,et al.  Elevated Circulating Stromal-Derived Factor-1 Levels in Sickle Cell Disease , 2009, Acta Haematologica.

[5]  A. Duits,et al.  Elevated endothelial progenitor cells during painful sickle cell crisis. , 2009, Experimental hematology.

[6]  A. Quyyumi,et al.  Bone marrow mobilization with granulocyte macrophage colony-stimulating factor improves endothelial dysfunction and exercise capacity in patients with peripheral arterial disease. , 2009, American heart journal.

[7]  S. Jackson,et al.  Erythrocyte Hemolysis and Hemoglobin Oxidation Promote Ferric Chloride-induced Vascular Injury* , 2009, Journal of Biological Chemistry.

[8]  C. Quinn,et al.  Prediction of adverse outcomes in children with sickle cell anemia: a study of the Dallas Newborn Cohort. , 2008, Blood.

[9]  D. Granger,et al.  SICKLE CELL DISEASE: ROLE OF REACTIVE OXYGEN AND NITROGEN METABOLITES , 2007, Clinical and experimental pharmacology & physiology.

[10]  M. Yoder,et al.  Human CD34+AC133+VEGFR-2+ cells are not endothelial progenitor cells but distinct, primitive hematopoietic progenitors. , 2007, Experimental hematology.

[11]  A. Duits,et al.  Serum levels of angiogenic factors indicate a pro‐angiogenic state in adults with sickle cell disease , 2006, British journal of haematology.

[12]  Stefanie Dimmeler,et al.  Impaired CXCR4 Signaling Contributes to the Reduced Neovascularization Capacity of Endothelial Progenitor Cells From Patients With Coronary Artery Disease , 2005, Circulation research.

[13]  D. Fliser,et al.  Stimulation of Endothelial Progenitor Cells: A New Putative Therapeutic Effect of Angiotensin II Receptor Antagonists , 2005, Hypertension.

[14]  K. Todd,et al.  Endothelial Progenitor Cells During Cerebrovascular Disease , 2005, Stroke.

[15]  H. Drexler,et al.  Statin-Induced Improvement of Endothelial Progenitor Cell Mobilization, Myocardial Neovascularization, Left Ventricular Function, and Survival After Experimental Myocardial Infarction Requires Endothelial Nitric Oxide Synthase , 2004, Circulation.

[16]  D. Fliser,et al.  Endothelial progenitor cell proliferation and differentiation is regulated by erythropoietin Rapid Communication , 2003 .

[17]  A. Quyyumi,et al.  Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. , 2003, The New England journal of medicine.

[18]  G. Gurtner,et al.  Human Endothelial Progenitor Cells From Type II Diabetics Exhibit Impaired Proliferation, Adhesion, and Incorporation Into Vascular Structures , 2002, Circulation.

[19]  Scott T. Miller,et al.  Prediction of adverse outcomes in children with sickle cell disease. , 2000, The New England journal of medicine.

[20]  E. Wayner,et al.  Circulating activated endothelial cells in sickle cell anemia. , 1997, The New England journal of medicine.

[21]  M. Gladwin,et al.  Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes. , 2007, Blood reviews.

[22]  L. Tavazzi,et al.  Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction. , 2005, Blood.

[23]  Frank J T Staal,et al.  Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. , 2004, Diabetes.

[24]  D. Fliser,et al.  Endothelial progenitor cell proliferation and differentiation is regulated by erythropoietin. , 2003, Kidney international.

[25]  R. Hebbel,et al.  Sickle cell anemia as a possible state of enhanced anti-apoptotic tone: survival effect of vascular endothelial growth factor on circulating and unanchored endothelial cells. , 1999, Blood.