Novel Therapies Targeting the Endothelium in Sickle Cell Disease

REFERENCES

• Hebbel RP, Vercellotti GM. The endothelial biology of sickle cell disease. J Lab Clin Med. 1997;129(3):288–293.
   PubMed Web of Science ®Google Scholar
• Solovey A, Lin Y, Browne P, Choong S, Wayner E, Hebbel RP. Circulating activated endothelial cells in sickle cell anemia. N Engl J Med. 1997;337(22):1584–1590.
   PubMed Web of Science ®Google Scholar
• Phelan MW, Faller DV. Hypoxia decreases constitutive nitric oxide synthase transcript and protein in cultured endothelial cells. J Cell Physiol. 1996;167(3):469–476.
   PubMed Web of Science ®Google Scholar
• Shreeniwas R, Koga S, Karakurum M, . Hypoxia-mediated induction of endothelial cell interleukin-1 α. An autocrine mechanism promoting expression of leukocyte adhesion molecules on the vessel surface. J Clin Invest. 1992;90(6):2333–2339.
   Google Scholar
• Platt OS. Sickle cell anemia as an inflammatory disease. J Clin Invest. 2000;106(3):337–338.
   PubMed Web of Science ®Google Scholar
• Francis RB Jr, Haywood LJ. Elevated immunoreactive tumor necrosis factor and interleukin-1 in sickle cell disease. J Natl Med Assoc. 1992; 84(7):611–615.
   PubMed Web of Science ®Google Scholar
• Graido-Gonzalez E, Doherty JC, Bergreen EW, Organ G, Telfer M, McMillen MA. Plasma endothelin-1, cytokine, and prostaglandin E2 levels in sickle cell disease and acute vaso-occlusive sickle crisis. Blood. 1998;92(7):2551–2555.
   PubMed Web of Science ®Google Scholar
• Phelan M, Perrine SP, Brauer M, Faller DV. Sickle erythrocytes, after sickling, regulate the expression of the endothelin-1 gene and protein in human endothelial cells in culture. J Clin Invest. 1995;96(2):1145–1151.
   PubMed Web of Science ®Google Scholar
• Shiu YT, Udden MM, McIntire LV. Perfusion with sickle erythrocytes up-regulates ICAM-1 and VCAM-1 gene expression in cultured human endothelial cells. Blood. 2000;95(10):3232–3241.
   PubMed Web of Science ®Google Scholar
• Brown MD, Wick TM, Eckman JR. Activation of vascular endothelial cell adhesion molecule expression by sickle blood cells. Pediatr Pathol Mol Med. 2001;20(1):47–72.
   PubMed Web of Science ®Google Scholar
• Jison ML, Munson PJ, Barb JJ, . Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease. Blood. 2004;104(1):270–280.
   PubMed Web of Science ®Google Scholar
• Enenstein J, Milbauer L, Domingo E, . Proinflammatory phenotype with imbalance of KLF2 and RelA: risk of childhood stroke with sickle cell anemia. Am J Hematol. 2010;85(1):18–23.
   PubMed Web of Science ®Google Scholar
• Key NS, Slungaard A, Dandelet L, . Whole blood tissue factor procoagulant activity is elevated in patients with sickle cell disease. Blood. 1998;91(11):4216–4223.
   PubMed Web of Science ®Google Scholar
• Solovey A, Gui L, Key NS, Hebbel RP. Tissue factor expression by endothelial cells in sickle cell anemia. J Clin Invest. 1998;101(9):1899–1904.
   PubMed Web of Science ®Google Scholar
• de Jong K, Emerson RK, Butler J, Bastacky J, Mohandas N, Kuypers FA. Short survival of phosphatidylserine-exposing red blood cells in murine sickle cell anemia. Blood. 2001;98(5):1577–1584.
   PubMed Web of Science ®Google Scholar
• Kaul DK, Liu XD, Chang HY, Nagel RL, Fabry ME. Effect of fetal hemoglobin on microvascular regulation in sickle transgenic-knockout mice. J Clin Invest. 2004;114(8):1136–1145.
   PubMed Web of Science ®Google Scholar
• Banerjee T, Kuypers FA. Reactive oxygen species and phosphatidylserine externalization in murine sickle red cells. Br J Haematol. 2004;124(3):391–402.
   PubMed Web of Science ®Google Scholar
• Nath KA,Grande JP, Haggard JJ, . Oxidative stress and induction of heme oxygenase-1 in the kidney in sickle cell disease. Am J Pathol. 2001;158(3):893–903.
   PubMed Web of Science ®Google Scholar
• Reiter CD, Wang X, Tanus-Santos JE, . Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nat Med. 2002;8(12):1383–1389.
   PubMed Web of Science ®Google Scholar
• Aslan M, Freeman BA. Oxidases and oxygenases in regulation of vascular nitric oxide signaling and inflammatory responses. Immunol Res. 2002;26(1):107–118.
   PubMed Web of Science ®Google Scholar
• Morris CR, Poljakovic M, Lavrisha L, Machado L, Kuypers FA, Morris SM Jr. Decreased arginine bioavailability and increased serum arginase activity in asthma. Am J Respir Crit Care Med. 2004;170(2):148–153.
   PubMed Web of Science ®Google Scholar
• Gladwin MT, Crawford JH, Patel RP. The biochemistry of nitric oxide, nitrite, and hemoglobin: role in blood flow regulation. Free Radic Biol Med. 2004;36(6):707–717.
   PubMed Web of Science ®Google Scholar
• Osarogiagbon UR, Choong S, Belcher JD, Vercellotti GM, Paller MS, Hebbel RP. Reperfusion injury pathophysiology in sickle transgenic mice. Blood. 2000;96(1):314–320.
   PubMed Web of Science ®Google Scholar
• Klings ES, Farber HW. Role of free radicals in the pathogenesis of acute chest syndrome in sickle cell disease. Respir Res. 2001;2(5):280–285.
   PubMed Web of Science ®Google Scholar
• Brugnara C. Erythrocyte dehydration in pathophysiology and treatment of sickle cell disease. Curr Opin Hematol. 1995;2(2):132–138.
   PubMedGoogle Scholar
• Stocker JW, De Franceschi L, McNaughton-Smith GA, Corrocher R, Beuzard Y, Brugnara C. ICA-17043, a novel Gardos channel blocker, prevents sickled red blood cell dehydration in vitro and in vivo in SAD mice. Blood. 2003;101(6):2412–2418.
   PubMed Web of Science ®Google Scholar
• Ataga KI, Smith WR, De Castro LM, . Efficacy and safety of the Gardos channel blocker, senicapoc (ICA-17043), in patients with sickle cell anemia. Blood. 2008;111(8):3991–3997.
   PubMed Web of Science ®Google Scholar
• De Franceschi L, Beuzard Y, Jouault H, Brugnara C. Modulation of erythrocyte potassium chloride cotransport, potassium content, and density by dietary magnesium intake in transgenic SAD mouse. Blood. 1996;88(7):2738–2744.
   PubMed Web of Science ®Google Scholar
• De Franceschi L, Bachir D, Galacteros F, . Oral magnesium supplements reduce erythrocyte dehydration in patients with sickle cell disease. J Clin Invest. 1997;100(7):1847–1852.
   PubMed Web of Science ®Google Scholar
• De Franceschi L, Bachir D, Galacteros F, . Oral magnesium pidolate: effects of long-term administration in patients with sickle cell disease. Br J Haematol. 2000;108(2):284–289.
   PubMed Web of Science ®Google Scholar
• Hankins JS, Wynn LW, Brugnara C, Hillery CA, Li CS, Wang WC. Phase I study of magnesium pidolate in combination with hydroxycarbamide for children with sickle cell anaemia. Br J Haematol. 2008;140(1):80–85.
   PubMed Web of Science ®Google Scholar
• Charache S, Terrin ML, Moore RD, . Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. New Engl J Med. 1995;332(20):1317–1322.
   PubMed Web of Science ®Google Scholar
• Platt OS, Orkin SH, Dover G, Beardsley GP, Miller B, Nathan DG. Hydroxyurea enhances fetal hemoglobin production in sickle cell anemia. J Clin Invest. 1984;74(2):652–656.
   PubMed Web of Science ®Google Scholar
• Rodgers GP, Dover GJ, Noguchi CT, Schechter AN, Nienhuis AW. Hematologic responses of patients with sickle cell disease to treatment with hydroxyurea. N Engl J Med. 1990;322(15):1037–1045.
   PubMed Web of Science ®Google Scholar
• Steinberg MH, Lu ZH, Barton FB, Terrin ML, Charache S, Dover GJ. Fetal hemoglobin in sickle cell anemia: determinants of response to hydroxyurea. Multicenter Study of Hydroxyurea. Blood. 1997;89(3):1078–1088.
   PubMed Web of Science ®Google Scholar
• Steinberg MH. Pathophysiologically based drug treatment of sickle cell disease. Trends Pharmacol Sci. 2006;27(4):204–210.
   PubMed Web of Science ®Google Scholar
• DeSimone J, Heller P, Schimenti JC, Duncan CH. Fetal hemoglobin production in adult baboons by 5-azacytidine or by phenylhydrazine-induced hemolysis is associated with hypomethylation of globin gene DNA. Prog Clin Biol Res. 1983;134:489–500.
   PubMedGoogle Scholar
• DeSimone J, Biel M, Heller P. Maintenance of fetal hemoglobin (Hb F) elevations in the baboon by prolonged erythropoietic stress. Blood. 1982;60(2):519–523.
   PubMed Web of Science ®Google Scholar
• Dover GJ, Charache S, Boyer SH, Vogelsang G, Moyer M. 5-Azacytidine increases Hb F production and reduces anemia in sickle cell disease: dose-response analysis of subcutaneous and oral dosage regimens. Blood. 1985;66(3):527–532.
   PubMed Web of Science ®Google Scholar
• Ley TJ, DeSimone J, Noguchi CT, . 5-Azacytidine increases γ-globin synthesis and reduces the proportion of dense cells in patients with sickle cell anemia. Blood. 1983;62(2):370–380.
   PubMed Web of Science ®Google Scholar
• DeSimone J, Koshy M, Dorn L, . Maintenance of elevated fetal hemoglobin levels by decitabine during dose interval treatment of sickle cell anemia. Blood. 2002;99(11):3905–3908.
   PubMed Web of Science ®Google Scholar
• Koshy M, Dorn L, Bressler L, . 2-Deoxy 5-azacytidine and fetal hemoglobin induction in sickle cell anemia. Blood. 2000;96(7):2379–2384.
   PubMed Web of Science ®Google Scholar
• Saunthararajah Y, Hillery CA, Lavelle D, . Effects of 5-aza-2′-deoxycytidine on fetal hemoglobin levels, red cell adhesion, and hematopoietic differentiation in patients with sickle cell disease. Blood. 2003;102(12):3865–3870.
   PubMed Web of Science ®Google Scholar
• Atweh GF, Sutton M, Nassif I, . Sustained induction of fetal hemoglobin by pulse butyrate therapy in sickle cell disease. Blood. 1999;93(6):1790–1797.
   PubMed Web of Science ®Google Scholar
• McMahon L,Tamary H, Askin M, . A randomized phase II trial of arginine butyrate with standard local therapy in refractory sickle cell leg ulcers. Br J Haematol. 2010;151(5):516–524.
   PubMed Web of Science ®Google Scholar
• Hebbel RP, Vercellotti GM, Pace BS, . The HDAC inhibitors trichostatin A and suberoylanilide hydroxamic acid exhibit multiple modalities of benefit for the vascular pathobiology of sickle transgenic mice. Blood. 2010;115(12):2483–2490.
   PubMed Web of Science ®Google Scholar
• Embury SH, Matsui NM, Ramanujam S, . The contribution of endothelial cell P-selectin to the microvascular flow of mouse sickle erythrocytes in vivo. Blood. 2004;104(10):3378–3385.
   PubMed Web of Science ®Google Scholar
• Matsui NM, Borsig L, Rosen SD, Yaghmai M, Varki A, Embury SH. P-selectin mediates the adhesion of sickle erythrocytes to the endothelium. Blood. 2001;98(6):1955–1962.
   PubMed Web of Science ®Google Scholar
• Chang J, Patton JT, Sarkar A, Ernst B, Magnani JL, Frenette PS. GMI-1070, a novel pan-selectin antagonist, reverses acute vascular occlusions in sickle cell mice. Blood. 2010;116(10):1779–1786.
   PubMed Web of Science ®Google Scholar
• Wun T, De Castro L, Styles L, . Effects of GMI-1070, a pan-selectin inhibitor, on leukocyte adhesion in sickle cell disease: results from a phase 1/2 study. Blood. 2010;116(21):262a.
   Web of Science ®Google Scholar
• Matsui NM,Varki A, Embury SH. Heparin inhibits the flow adhesion of sickle red blood cells to P-selectin. Blood. 2002;100(10):3790–3796.
   PubMed Web of Science ®Google Scholar
• Qari MH, Aljaouni SK, Alardawi MS, . Reduction of painful vaso-occlusive crisis of sickle cell anaemia by tinzaparin in a double-blind randomized trial. Thromb Haemost. 2007;98(2):392–396.
   PubMed Web of Science ®Google Scholar
• Finnegan EM, Barabino GA, Liu XD, Chang HY, Jonczyk A, Kaul DK. Small-molecule cyclic αVβ3 antagonists inhibit sickle red cell adhesion to vascular endothelium and vasoocclusion. Am J Physiol Heart Circ Physiol. 2007;293(2):H1038–H1045.
   PubMed Web of Science ®Google Scholar
• Kaul DK, Tsai HM, Liu XD, Nakada MT, Nagel RL, Coller BS. Monoclonal antibodies to αVβ3 (7E3 and LM609) inhibit sickle red blood cell-endothelium interactions induced by platelet-activating factor. Blood. 2000;95(2):368–374.
   PubMed Web of Science ®Google Scholar
• Zennadi R, Moeller BJ, Whalen EJ, . Epinephrine-induced activation of LW-mediated sickle cell adhesion and vaso-occlusion in vivo. Blood. 2007;110(7):2708–2717.
   PubMed Web of Science ®Google Scholar
• Lee SP, Ataga KI, Zayed M, . Phase I study of eptifibatide in patients with sickle cell anaemia. Br J Haematol. 2007;139(4):612–620.
   PubMed Web of Science ®Google Scholar
• Belcher JD, Marker PH, Weber JP, Hebbel RP, Vercellotti GM. Activated monocytes in sickle cell disease: potential role in the activation of vascular endothelium and vaso-occlusion. Blood. 2000;96(7):2451–2459.
   PubMed Web of Science ®Google Scholar
• Kollander R, Solovey A, Milbauer LC, Abdulla F, Kelm RJ Jr, Hebbel RP. Nuclear factor-κ B (NFκB) component p50 in blood mononuclear cells regulates endothelial tissue factor expression in sickle transgenic mice: implications for the coagulopathy of sickle cell disease. Transl Res. 2010;155(4):170–177.
   PubMed Web of Science ®Google Scholar
• Kaul DK, Liu XD, Choong S, Belcher JD, Vercellotti GM, Hebbel RP. Anti-inflammatory therapy ameliorates leukocyte adhesion and microvascular flow abnormalities in transgenic sickle mice. Am J Physiol Heart Circ Physiol. 2004;287(1):H293–H301.
   PubMed Web of Science ®Google Scholar
• Solovey AA, Solovey AN, Harkness J, Hebbel RP. Modulation of endothelial cell activation in sickle cell disease: a pilot study. Blood. 2001;97(7):1937–1941.
   PubMed Web of Science ®Google Scholar
• Solovey A, Kollander R, Shet A, . Endothelial cell expression of tissue factor in sickle mice is augmented by hypoxia/reoxygenation and inhibited by lovastatin. Blood. 2004;104(3):840–846.
   PubMed Web of Science ®Google Scholar
• Kato GJ, Hunter C, Hunter L, . Atorvastatin therapy restores nitric oxide-dependent vascular responsiveness in patients with sickle cell disease. Blood. 2004;104(11):72a.
   Web of Science ®Google Scholar
• Hoppe CC, Stewart KR, Higa A, . The effect of simvastatin on markers of vascular dysfunction in patients with sickle cell disease. Blood. 2009;114:260a.
   Web of Science ®Google Scholar
• Niihara Y, Zerez CR, Akiyama DS, Tanaka KR. Oral L-glutamine therapy for sickle cell anemia: I. Subjective clinical improvement and favorable change in red cell NAD redox potential. Am J Hematol. 1998;58(2):117–121.
   Google Scholar
• Niihara Y, Matsui NM, Shen YM, . L-glutamine therapy reduces endothelial adhesion of sickle red blood cells to human umbilical vein endothelial cells. BMC Blood Disord. 2005;5:4.
   PubMedGoogle Scholar
• Williams R, Olivi S, Li CS, . Oral glutamine supplementation decreases resting energy expenditure in children and adolescents with sickle cell anemia. J Pediatr Hematol Oncol. 2004;26(10):619–625.
   PubMed Web of Science ®Google Scholar
• Tomer A, Kasey S, Connor WE, Clark S, Harker LA, Eckman JR. Reduction of pain episodes and prothrombotic activity in sickle cell disease by dietary n-3 fatty acids. Thromb Haemost. 2001;85(6):966–974.
   PubMed Web of Science ®Google Scholar
• Weiner DL, Hibberd PL, Betit P, Cooper AB, Botelho CA, Brugnara C. Preliminary assessment of inhaled nitric oxide for acute vaso-occlusive crisis in pediatric patients with sickle cell disease. JAMA. 2003;289(9):1136–1142.
   PubMed Web of Science ®Google Scholar
• Head CA, Swerdlow P, McDade WA, . Beneficial effects of nitric oxide breathing in adult patients with sickle cell crisis. Am J Hematol. 2010;85(10):800–802.
   PubMed Web of Science ®Google Scholar
• Dasgupta T, Hebbel RP, Kaul DK. Protective effect of arginine on oxidative stress in transgenic sickle mouse models. Free Radic Biol Med. 2006;41(12):1771–1780.
   PubMed Web of Science ®Google Scholar
• Kaul DK, Zhang X, Dasgupta T, Fabry ME. Arginine therapy of transgenic-knockout sickle mice improves microvascular function by reducing non-nitric oxide vasodilators, hemolysis, and oxidative stress. Am J Physiol Heart Circ Physiol. 2008;295(1):H39–H47.
   Web of Science ®Google Scholar
• Romero JR, Suzuka SM, Nagel RL, Fabry ME. Arginine supplementation of sickle transgenic mice reduces red cell density and Gardos channel activity. Blood. 2002;99(4):1103–1108.
   PubMed Web of Science ®Google Scholar
• Morris CR, Morris SM Jr, Hagar W, . Arginine therapy: a new treatment for pulmonary hypertension in sickle cell disease? Am J Respir Crit Care Med. 2003;168(1):63–69.
   PubMed Web of Science ®Google Scholar
• Morris CR, Kuypers FA, Larkin S, Vichinsky EP, Styles LA. Patterns of arginine and nitric oxide in patients with sickle cell disease with vaso-occlusive crisis and acute chest syndrome. J Pediatr Hematol Oncol. 2000;22(6):515–520.
   PubMed Web of Science ®Google Scholar
• Little JA, Hauser KP, Martyr SE, . Hematologic, biochemical, and cardiopulmonary effects of L-arginine supplementation or phosphodiesterase 5 inhibition in patients with sickle cell disease who are on hydroxyurea therapy. Eur J Haematol. 2009;82(4):315–321.
   PubMed Web of Science ®Google Scholar
• Styles LA. Nitric oxide effects in sickle cell disease. Blood. 2008;112:48a.
   Web of Science ®Google Scholar
• Gordeuk VR. Efficacy and safety of sildenafil in the treatment of severe pulmonary hypertension in patients with hemoglobinopathies. Haematologica. 2005;90(4):433–434.
   PubMed Web of Science ®Google Scholar
• Machado RF, Martyr S, Kato GJ, . Sildenafil therapy in patients with sickle cell disease and pulmonary hypertension. Br J Haematol. 2005;130(3):445–453.
   PubMed Web of Science ®Google Scholar
• Machado RF, Barst RJ, Yovetich NA, . Safety and efficacy of sildenafil therapy for Doppler-defined pulmonary hypertension in patients with sickle cell disease: preliminary results of the Walk-PHaSST clinical trial. Blood. 2009;114:571a.
   Web of Science ®Google Scholar
• Mack AK, McGowan VR, Tremonti CK, . Sodium nitrite promotes regional blood flow in patients with sickle cell disease: a phase I/II study. Br J Haematol. 2008;142(6):971–978.
   PubMed Web of Science ®Google Scholar
• Yuditskaya S,Tumblin A, Hoehn GT, . Proteomic identification of altered apolipoprotein patterns in pulmonary hypertension and vasculopathy of sickle cell disease. Blood. 2009;113(5):1122–1128.
   PubMed Web of Science ®Google Scholar
• Hsu L, Ataga KI, Gordeuk VR, . Tetrahydrobiopterin (6R-BH4): novel therapy for endothelial dysfunction in sickle cell disease. Blood. 2008;112:5a.
   PubMed Web of Science ®Google Scholar
• Sabaa N, de Franceschi L, Bonnin P, . Endothelin receptor antagonism prevents hypoxia-induced mortality and morbidity in a mouse model of sickle-cell disease. J Clin Invest. 2008;118(5):1924–1933.
   PubMed Web of Science ®Google Scholar
• Hammerman SI, Kourembanas S, Conca TJ, Tucci M, Brauer M, Farber H W. Endothelin-1 production during the acute chest syndrome in sickle cell disease. Am J Resp Crit Care Med. 1997;156(1):280–285.
   PubMed Web of Science ®Google Scholar
• Werdehoff SG, Moore RB, Hoff CJ, Fillingim E, Hackman AM. Elevated plasma endothelin-1 levels in sickle cell anemia: relationships to oxygen saturation and left ventricular hypertrophy. Am J Hematol. 1998;58(3):195–199.
   PubMed Web of Science ®Google Scholar
• Barst RJ, Mubarak KK, Machado RF, . Exercise capacity and haemodynamics in patients with sickle cell disease with pulmonary hypertension treated with bosentan: results of the ASSET studies. Br J Haematol. 2010;149(3):426–435.
   PubMed Web of Science ®Google Scholar
• Minniti CP, Machado RF, Coles WA, Sachdev V, Gladwin MT, Kato GJ. Endothelin receptor antagonists for pulmonary hypertension in adult patients with sickle cell disease. Br J Haematol. 2009;147(5):737–743.
   PubMed Web of Science ®Google Scholar