Research Topics
Genomes and Genes | Mark T GladwinSummaryAffiliation: University of Pittsburgh Country: USA Publications
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Publications
The relationship between the severity of hemolysis, clinical manifestations and risk of death in 415 patients with sickle cell anemia in the US and EuropeMehdi Nouraie
Howard University, Washington, USA
Haematologica 98:464-72. 2013..These results confirm associations between hemolytic rate and pulse pressure, oxygen saturation, increases in Doppler-estimated pulmonary systolic pressures and mortality (Clinicaltrials.gov identifier: NCT00492531)...
Pulmonary complications of sickle cell diseaseAndrew C Miller
Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Medical Center, 3459 Fifth Avenue, Pittsburgh, PA 15213, USA
Am J Respir Crit Care Med 185:1154-65. 2012..Clinicians should be vigilant in screening and treating such comorbidities to improve patient outcomes...- Hemolysis and cell-free hemoglobin drive an intrinsic mechanism for human diseaseMark T Gladwin
Vascular Medicine Institute and Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
J Clin Invest 122:1205-8. 2012.... - Cardiovascular abnormalities in sickle cell diseaseMark T Gladwin
Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, 3459 Fifth Avenue, Montefiore Hospital, Pittsburgh, PA 15213, USA
J Am Coll Cardiol 59:1123-33. 2012..Sudden death is an increasingly recognized problem, and further cardiac investigations are necessary to recognize and treat high-risk patients... - Storage lesion in banked blood due to hemolysis-dependent disruption of nitric oxide homeostasisMark T Gladwin
Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
Curr Opin Hematol 16:515-23. 2009..However, the degree of intravascular hemolysis and microparticle formation in humans post-transfusion due to both storage and physiological shear has not been well studied... - The new chemical biology of nitrite reactions with hemoglobin: R-state catalysis, oxidative denitrosylation, and nitrite reductase/anhydraseMark T Gladwin
Pulmonary and Vascular Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Acc Chem Res 42:157-67. 2009..We consider how these reactions may contribute to physiological and pathological hypoxic signaling... - Nitric oxide for inhalation in the acute treatment of sickle cell pain crisis: a randomized controlled trialMark T Gladwin
Division of Pulmonary, Allergy, and Critical Care Medicine, Vascular Medicine Institute, University of Pittsburgh, 3459 Fifth Ave, 628 NW, Pittsburgh, PA 15213
JAMA 305:893-902. 2011..Inhaled nitric oxide has shown evidence of efficacy in mouse models of sickle cell disease (SCD), case series of patients with acute chest syndrome, and 2 small placebo-controlled trials for treatment of vaso-occlusive pain crisis (VOC)... - Prevalence, risk factors and mortality of pulmonary hypertension defined by right heart catheterization in patients with sickle cell diseaseMark T Gladwin
Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA
Expert Rev Hematol 4:593-6. 2011..The presence of pulmonary hypertension diagnosed by echocardiography or right heart catheterization indicates a significant and independent risk factor for prospective mortality... - Nitrite reductase activity of hemoglobin as a systemic nitric oxide generator mechanism to detoxify plasma hemoglobin produced during hemolysisPeter C Minneci
Department of Surgery, The Children s Institute for Surgical Science, The Children s Hospital of Philadelphia, PA, USA
Am J Physiol Heart Circ Physiol 295:H743-54. 2008..Nitrite infusions may promote NO generation from Hb while maintaining oxygen delivery; this effect could be harnessed to treat hemolytic conditions and to detoxify Hb-based blood substitutes... 
Nitrite infusion in humans and nonhuman primates: endocrine effects, pharmacokinetics, and tolerance formationAndre Dejam
Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Circulation 116:1821-31. 2007..However, important questions of potency, kinetics, mechanism of action, and possible induction of tolerance remain unanswered...- 14-3-3 binding and phosphorylation of neuroglobin during hypoxia modulate six-to-five heme pocket coordination and rate of nitrite reduction to nitric oxideThottala Jayaraman
Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
J Biol Chem 286:42679-89. 2011..Hypoxia-regulated reactions of nitrite and neuroglobin may contribute to the cellular adaptation to hypoxia... - Hemodynamic and functional assessment of patients with sickle cell disease and pulmonary hypertensionAnastasia Anthi
Vascular Medicine Branch, Clinical Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 2089, USA
Am J Respir Crit Care Med 175:1272-9. 2007..Although pulmonary hypertension (PH) is a common complication of sickle cell disease (SCD) associated with high mortality, there exist few data characterizing hemodynamics and cardiopulmonary function in this population... - Hematologic, biochemical, and cardiopulmonary effects of L-arginine supplementation or phosphodiesterase 5 inhibition in patients with sickle cell disease who are on hydroxyurea therapyJane A Little
Pulmonary and Vascular Medicine Branch, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892 1476, USA
Eur J Haematol 82:315-21. 2009..L-arginine, an NO precursor, and the phosphodiesterase (PDE) 5 inhibitor sildenafil, which potentiates cGMP, were studied in adults with sickle cell disease (SCD) who were stably on HU... - Biological activity of nitric oxide in the plasmatic compartmentXunde Wang
Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1662, USA
Proc Natl Acad Sci U S A 101:11477-82. 2004..The studies further suggest that alternative NO reaction end products in plasma, such as nitrite, N-nitrosamines, iron-nitrosyls, and nitrated lipids, should be evaluated in blood NO transport along the vasculature... - Evolution of novel small-molecule therapeutics targeting sickle cell vasculopathyGregory J Kato
Critical Care Medicine Department, Clinical Center, National Institutes of Health, 10 Center Dr, MSC 1476, Bldg 10 CRC, Room 5 5140, Bethesda, MD 20892 1476, USA
JAMA 300:2638-46. 2008..This article reviews the pathophysiology of sickle vasculopathy and the results of preliminary clinical trials of novel small-molecule therapeutics directed at abnormal vascular biology in patients with sickle cell disease... - Severity of pulmonary hypertension during vaso-occlusive pain crisis and exercise in patients with sickle cell diseaseRoberto F Machado
Vascular Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1476, USA
Br J Haematol 136:319-25. 2007..001) in all subjects. These data suggest that acute elevations in pulmonary pressures during VOC or exercise may contribute to morbidity and mortality in patients with sickle cell disease... - Concerted nitric oxide formation and release from the simultaneous reactions of nitrite with deoxy- and oxyhemoglobinRozalina Grubina
Vascular Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 282:12916-27. 2007.... - Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric controlZhi Huang
Vascular Therapeutics Section, Cardiovascular Branch, National Heart, Lung and Blood Institute, and Laboratory of Chemical Biology, National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892-1662, USA
J Clin Invest 115:2099-107. 2005..These data suggest that the oxygen sensor for hypoxic vasodilation is determined by Hb oxygen saturation and quaternary structure and that the nitrite reductase activity of Hb generates NO gas under allosteric and pH control... - Platelet activation in patients with sickle disease, hemolysis-associated pulmonary hypertension, and nitric oxide scavenging by cell-free hemoglobinJose Villagra
Vascular Medicine Branch of National Heart, Lung, and Blood Institute, Clinical Center, National Institutes of Health, Bethesda, MD 20892 1476, USA
Blood 110:2166-72. 2007..This supports a role for NO-based therapeutics for SCD vasculopathy. This trial was registered at www.clinicaltrials.gov as no. NCT00352430... - Dietary nitrate and nitrite modulate blood and organ nitrite and the cellular ischemic stress responseNicolaas J H Raat
Pulmonary and Vascular Medicine Branch, National Heart, Lung, and Blood Institute, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA
Free Radic Biol Med 47:510-7. 2009.... - Nitrite reductase activity of hemoglobin S (sickle) provides insight into contributions of heme redox potential versus ligand affinityRozalina Grubina
Vascular Medicine Branch, NHLBI, National Institutes of Health, Bethesda, MD 20892, USA
J Biol Chem 283:3628-38. 2008..From a pathophysiological standpoint, under conditions where HbS polymers form, the rate of nitrite reduction is reduced compared with HbA and solution-phase HbS, indicating that HbS polymers reduce nitrite more slowly... - Nitrite anion provides potent cytoprotective and antiapoptotic effects as adjunctive therapy to reperfusion for acute myocardial infarctionFelix M Gonzalez
Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1061, USA
Circulation 117:2986-94. 2008.... - Segmentation and quantification of pulmonary artery for noninvasive CT assessment of sickle cell secondary pulmonary hypertensionMarius George Linguraru
Radiology and Imaging Sciences, Clinical Center National Institutes of Health, Bethesda, Maryland 20892, USA
Med Phys 37:1522-32. 2010..The authors propose a semiautomated computer-assisted diagnostic (CAD) tool to quantify the main PA size from pulmonary CT angiography (CTA)... - Ceruloplasmin is a NO oxidase and nitrite synthase that determines endocrine NO homeostasisSruti Shiva
Vascular Medicine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Nat Chem Biol 2:486-93. 2006.... - Deoxymyoglobin is a nitrite reductase that generates nitric oxide and regulates mitochondrial respirationSruti Shiva
Vascular Medicine Branch, Clinical Center National Institutes of Health, Bethesda, MD 20892 1662, USA
Circ Res 100:654-61. 2007.... - Sodium nitrite promotes regional blood flow in patients with sickle cell disease: a phase I/II studyA Kyle Mack
Pulmonary and Vascular Medicine Branch, National Heart, Lung and Blood Institute National Institutes of Health, Bethesda, MD, USA
Br J Haematol 142:971-8. 2008..The unique pharmacological properties of nitrite as a hypoxia-potentiated vasodilator and cytoprotective agent in the setting of ischaemia-reperfusion injury make this anion a plausible NO donor for future clinical trials in SCD... - Erythrocytes are the major intravascular storage sites of nitrite in human bloodAndre Dejam
Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD 20892, USA
Blood 106:734-9. 2005..These studies suggest a dynamic intravascular NO metabolism in which endothelial NOS-derived NO is stabilized as nitrite, transported by erythrocytes, and consumed during arterial-to-venous transit... - Endothelin receptor antagonists for pulmonary hypertension in adult patients with sickle cell diseaseCaterina P Minniti
Pulmonary and Vascular Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Br J Haematol 147:737-43. 2009..Therapy was stopped in two patients who were switched then to the other ETR blocker agent. These data suggest preliminary evidence for the benefit of bosentan and ambrisentan in pulmonary hypertension in SCD... - Amplified expression profiling of platelet transcriptome reveals changes in arginine metabolic pathways in patients with sickle cell diseaseNalini Raghavachari
Vascular Medicine Branch, National Heart, Lung, and Blood Institute National Institutes of Health, Bethesda, MD 20892 1454, USA
Circulation 115:1551-62. 2007..Recent functional studies of platelets in patients with sickle cell disease reveal a basally activated state, which suggests that pathological platelet activation may contribute to sickle cell disease vasculopathy... - Interferon-gamma induces p11 gene and protein expression in human epithelial cells through interferon-gamma-activated sequences in the p11 promoterXiu li Huang
Critical Care Medicine Department of the Warren G Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 278:9298-308. 2003.... - Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulationKenyatta Cosby
Cardiovascular Branch, National Heart, Lung and Blood Institute, National Institutes of Health, 10 Center Drive, Building 10, Room 7B15 Bethesda, Maryland 20892, USA
Nat Med 9:1498-505. 2003..These results suggest that nitrite represents a major bioavailable pool of NO, and describe a new physiological function for hemoglobin as a nitrite reductase, potentially contributing to hypoxic vasodilation... - Inhaled nebulized nitrite is a hypoxia-sensitive NO-dependent selective pulmonary vasodilatorChristian J Hunter
Critical Care Medicine Department, Clinical Center, National Heart, Lung and Blood Institute, National Institutes of Health, 10 Center Drive, Bethesda, Maryland 20892-1662, USA
Nat Med 10:1122-7. 2004.... - Divergent nitric oxide bioavailability in men and women with sickle cell diseaseMark T Gladwin
Critical Care Medicine Department, Warren G Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892 1662, USA
Circulation 107:271-8. 2003..Although reduced endothelial nitric oxide (NO) bioavailability has been demonstrated in arteriosclerotic vascular disease, the integrity of this system in sickle cell disease remains uncertain... - Nitric oxide scavenging by red blood cell microparticles and cell-free hemoglobin as a mechanism for the red cell storage lesionChenell Donadee
Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA
Circulation 124:465-76. 2011.... - Normoxic cyclic GMP-independent oxidative signaling by nitrite enhances airway epithelial cell proliferation and wound healingLing Wang
Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA
Nitric Oxide 26:203-10. 2012.... - The emerging biology of the nitrite anionMark T Gladwin
Vascular Medicine Branch, National Heart, Lung, and Blood Institute, US National Institutes of Health, Bethesda, Maryland, USA
Nat Chem Biol 1:308-14. 2005..A recent two-day symposium at the US National Institutes of Health highlighted recent advances in the understanding of nitrite biochemistry, physiology and therapeutics... - Nitrite as a vascular endocrine nitric oxide reservoir that contributes to hypoxic signaling, cytoprotection, and vasodilationMark T Gladwin
Vascular Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 1454, USA
Am J Physiol Heart Circ Physiol 291:H2026-35. 2006..An expanded consideration of nitrite as a hypoxia-dependent intrinsic signaling molecule has opened up a new field of research and therapeutic opportunities for diseases associated with regional hypoxia and vasoconstriction... - Increased pulmonary pressures and myocardial wall stress in children with severe malariaJacqueline J Janka
Clinical Center Critical Care Medicine Department and Pulmonary and Vascular Medicine and Translational Medicine Branches, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Infect Dis 202:791-800. 2010..To test whether this pathophysiology occurs in malaria, we examined in Mali 53 children who were admitted to the hospital with severe malaria (excluding cerebral malaria) and 31 age-matched controls... - Endothelial progenitor cell mobilization and increased intravascular nitric oxide in patients undergoing cardiac rehabilitationJonathan D Paul
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
J Cardiopulm Rehabil Prev 27:65-73. 2007.... - Echocardiographic markers of elevated pulmonary pressure and left ventricular diastolic dysfunction are associated with exercise intolerance in adults and adolescents with homozygous sickle cell anemia in the United States and United KingdomVandana Sachdev
Cardiovascular and Pulmonary Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, USA
Circulation 124:1452-60. 2011.... - Plasma thrombospondin-1 is increased during acute sickle cell vaso-occlusive events and associated with acute chest syndrome, hydroxyurea therapy, and lower hemolytic ratesEnrico M Novelli
Division of Hematology Oncology, University of Pittsburgh Medical Center UPMC, Vascular Medicine Institute VMI, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Am J Hematol 87:326-30. 2012..Our results suggest that TSP1 levels are associated with more VOE, hydroxyurea use and lower rates of hemolysis. High TSP1 concentrations may indicate higher risk of the viscosity/vaso-occlusion phenotype of SCD... - Hemolysis-associated endothelial dysfunction mediated by accelerated NO inactivation by decompartmentalized oxyhemoglobinPeter C Minneci
Critical Care Medicine Department, NIH, Bethesda, Maryland 20892, USA
J Clin Invest 115:3409-17. 2005.... - Chronic hyper-hemolysis in sickle cell anemia: association of vascular complications and mortality with less frequent vasoocclusive painJames G Taylor
Pulmonary and Vascular Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, United States of America
PLoS ONE 3:e2095. 2008..We have previously reported that intense hemolysis is associated with increased risk of vascular complications in a small cohort of adults with sickle cell disease. These observations have not been validated in other populations... - Copper dependence of the biotin switch assay: modified assay for measuring cellular and blood nitrosated proteinsXunde Wang
Pulmonary and Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Free Radic Biol Med 44:1362-72. 2008..The addition of copper to ascorbate allows for a simple assay modification that dramatically increases sensitivity while maintaining specificity... - Levels of soluble endothelium-derived adhesion molecules in patients with sickle cell disease are associated with pulmonary hypertension, organ dysfunction, and mortalityGregory J Kato
Vascular Therapeutics Section, Cardiovascular Branch, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA
Br J Haematol 130:943-53. 2005..Our data are consistent with steady state levels of soluble adhesion molecules as markers of pulmonary hypertension and risk of death... - Characterization of erythrocytic uptake and release and disposition pathways of nitrite, nitrate, methemoglobin, and iron-nitrosyl hemoglobin in the human circulationYuen Yi Hon
Clinical Center Pharmacy Department, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
Drug Metab Dispos 38:1707-13. 2010.... - The biochemistry of nitric oxide, nitrite, and hemoglobin: role in blood flow regulationMark T Gladwin
Critical Care Medicine Department, Clinical Center, Laboratory of Chemical Biology, National Institutes of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 1662, USA
Free Radic Biol Med 36:707-17. 2004..This newly described role of hemoglobin as a nitrite reductase is discussed in the context of blood flow regulation, oxygen sensing, and nitrite-based therapeutics... - Role of the red blood cell in nitric oxide homeostasis and hypoxic vasodilationMark T Gladwin
Vascular Medicine Branch, National Heart, Lung and Blood Institute National Institutes of Health, Bethesda, Maryland 20892 1454, USA
Adv Exp Med Biol 588:189-205. 2006..The later newly described role of hemoglobin as a nitrite reductase is discussed in the context of hypoxic vasodilation, blood flow regulation and oxygen sensing... - The detection of the nitrite reductase and NO-generating properties of haemoglobin by mitochondrial inhibitionSruti Shiva
Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA
Cardiovasc Res 89:566-73. 2011..Here, we characterize the NO-generating properties of Hb using the cGMP-independent and NO-dependent inhibition of mitochondrial cytochrome c oxidase... - Nitrite potently inhibits hypoxic and inflammatory pulmonary arterial hypertension and smooth muscle proliferation via xanthine oxidoreductase-dependent nitric oxide generationBrian S Zuckerbraun
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
Circulation 121:98-109. 2010..Considering the fact that nitric oxide exhibits vasoprotective properties, we examined the effects of nitrite on experimental pulmonary arterial hypertension... - Heme oxygenase-1 deficiency accelerates formation of arterial thrombosis through oxidative damage to the endothelium, which is rescued by inhaled carbon monoxideAndrea L True
National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892, USA
Circ Res 101:893-901. 2007..Induction of HO-1 may be beneficial in the prevention of thrombosis associated with vascular oxidant stress and inflammation... - Human neuroglobin functions as a redox-regulated nitrite reductaseMauro Tiso
Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
J Biol Chem 286:18277-89. 2011..We hypothesize that the six-coordinate heme globin superfamily may subserve a function as primordial hypoxic and redox-regulated NO-signaling proteins... - Lopinavir-ritonavir: effects on endothelial cell function in healthy subjectsJessica R Grubb
Critical Care Medical Department, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA
J Infect Dis 193:1516-9. 2006..Thus, in this small cohort of subjects, short-term treatment with lopinavir-ritonavir does not appear to directly promote endothelial cell dysfunction... - Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transferSruti Shiva
Vascular Medicine Branch, National Heart Lung Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Exp Med 204:2089-102. 2007..These data suggest that nitrite dynamically modulates mitochondrial resilience to reperfusion injury and may represent an effector of the cell-survival program of ischemic preconditioning and the Mediterranean diet... - Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell diseaseChristopher D Reiter
Critical Care Medicine Department of the Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
Nat Med 8:1383-9. 2002..Decompartmentalization of hemoglobin and subsequent dioxygenation of nitric oxide may explain the vascular complications shared by acute and chronic hemolytic disorders... - Low NO concentration dependence of reductive nitrosylation reaction of hemoglobinJesús Tejero
Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
J Biol Chem 287:18262-74. 2012..The observed fast reductive nitrosylation observed at low NO concentrations may function to preserve NO bioactivity via primary oxidation of NO to form nitrite or in the presence of nitrite to form N(2)O(3) and S-nitrosothiols... - Nitrite-generated NO circumvents dysregulated arginine/NOS signaling to protect against intimal hyperplasia in Sprague-Dawley ratsMatthew J Alef
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
J Clin Invest 121:1646-56. 2011..The vasoprotective effects of nitrite were counteracted by inhibition of XOR. These data illustrate the importance of nitrite-generated NO as an endogenous adaptive response and as a pathway that can be harnessed for therapeutic benefit... - Methodologies for the sensitive and specific measurement of S-nitrosothiols, iron-nitrosyls, and nitrite in biological samplesBenjamin K Yang
Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892-1662, USA
Free Radic Res 37:1-10. 2003 - Diastolic dysfunction is an independent risk factor for death in patients with sickle cell diseaseVandana Sachdev
Cardiovascular Branch, Echocardiography Laboratory, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892 1454, USA
J Am Coll Cardiol 49:472-9. 2007..The goal of this study was to characterize left ventricular diastolic function in the sickle cell disease (SCD) population and to relate echocardiographic measures of dysfunction with pulmonary hypertension and mortality... - Sickle cell disease vasculopathy: a state of nitric oxide resistanceKatherine C Wood
Vascular Medicine Branch, National Heart Lung Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Free Radic Biol Med 44:1506-28. 2008..New therapeutic strategies to limit intravascular hemolysis and ROS generation and increase NO bioavailability are discussed... - Imaging hemoglobin oxygen saturation in sickle cell disease patients using noninvasive visible reflectance hyperspectral techniques: effects of nitric oxideKarel J Zuzak
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases/NIH, 9000 Rockville Pike, Bethesda, MD 20892-0510, USA
Am J Physiol Heart Circ Physiol 285:H1183-9. 2003.... - Mutations and polymorphisms in hemoglobin genes and the risk of pulmonary hypertension and death in sickle cell diseaseJames G Taylor
Vascular Medicine Branch, NHLBI, NIH, Bethesda, Maryland 20892 1476, USA
Am J Hematol 83:6-14. 2008..Despite this protective association, patients with SC who did develop pulmonary hypertension remained at significant risk for death during 49 months of follow-up (Hazard Ratio=8.20, P=0.0057)... - Markers of severe vaso-occlusive painful episode frequency in children and adolescents with sickle cell anemiaDeepika S Darbari
Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
J Pediatr 160:286-90. 2012.... - Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell diseaseGregory J Kato
Vascular Medicine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, 10 Center Dr, MSC 1476, Bldg 10CRC, Rm 5 5140, Bethesda, MD 20892, USA
Blood 107:2279-85. 2006..We propose that LDH elevation identifies patients with a syndrome of hemolysis-associated NO resistance, endothelial dysfunction, and end-organ vasculopathy... - N-terminal pro-brain natriuretic peptide levels and risk of death in sickle cell diseaseRoberto F Machado
Vascular Medicine Branch, Clinical Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1454, USA
JAMA 296:310-8. 2006..Levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) provide such information in patients with idiopathic pulmonary arterial hypertension... - The functional nitrite reductase activity of the heme-globinsMark T Gladwin
Pulmonary and Vascular Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, USA
Blood 112:2636-47. 2008..We will review these reactions in the biologic framework of hypoxic signaling in blood and the heart... - Cerebrovascular disease associated with sickle cell pulmonary hypertensionGregory J Kato
Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 1476, USA
Am J Hematol 81:503-10. 2006..Clinicians should suspect occult cerebrovascular disease in sickle cell patients with pulmonary hypertension... - S-Nitrosohemoglobin is unstable in the reductive erythrocyte environment and lacks O2/NO-linked allosteric functionMark T Gladwin
Critical Care Medicine Department, Warren G Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892 1662, USA
J Biol Chem 277:27818-28. 2002.... - Hemolytic anemia-associated pulmonary hypertension in sickle cell diseaseElaina E Lin
National Institutes of Health, 31 Center Drive, Bethesda, MD 20892, USA
Curr Hematol Rep 4:117-25. 2005..Finally, we review suggested therapies including the established treatments and new pulmonary vasodilator and remodeling agents in the management of pulmonary hypertension in hemolytic anemias... - Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypesGregory J Kato
Vascular Medicine Branch, National Heart, Lung and Blood Institute, Critical Care Medicine Department, Clinical Center, National Institutes of Health, 10 Center Drive, Building 10CRC 5 5140, Bethesda, MD 20892 1476, USA
Blood Rev 21:37-47. 2007..Some of these drugs are now being studied in clinical trials... - Myocardial protection by nitrite: evidence that this reperfusion therapeutic will not be lost in translationShashank S Sinha
Pulmonary and Vascular Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA
Trends Cardiovasc Med 18:163-72. 2008.... - Nitrite infusions to prevent delayed cerebral vasospasm in a primate model of subarachnoid hemorrhageRyszard M Pluta
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
JAMA 293:1477-84. 2005..Decreased bioavailability of nitric oxide has been associated with the development of cerebral vasospasm... - Severe pulmonary hypertension in an adolescent with sickle cell diseaseJames G Taylor
Vascular Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892-1476, USA
Am J Hematol 83:71-2. 2008 - An emerging role for nitric oxide in sickle cell disease vascular homeostasis and therapyChristopher D Reiter
Critical Care Medicine Department, Warren G Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1662, USA
Curr Opin Hematol 10:99-107. 2003..Possible effects of chronic nitric oxide-based therapies on erythrocyte density, pulmonary artery pressures, and fetal hemoglobin induction deserve study... - Sildenafil therapy in patients with sickle cell disease and pulmonary hypertensionRoberto F Machado
Vascular Therapeutics Section, Cardiovascular Branch, National Heart Lung and Blood Institute, Bethesda, MD, USA
Br J Haematol 130:445-53. 2005.... - Role of the anion nitrite in ischemia-reperfusion cytoprotection and therapeuticsCameron Dezfulian
Vascular Medicine Branch, National Heart Lung Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Cardiovasc Res 75:327-38. 2007.... - Pulmonary hypertension as a risk factor for death in patients with sickle cell diseaseMark T Gladwin
Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892 1662, USA
N Engl J Med 350:886-95. 2004..The prevalence of pulmonary hypertension in adults with sickle cell disease, the mechanism of its development, and its prospective prognostic significance are unknown... - Pulmonary vascular lesions are common in SIV- and SHIV-env-infected macaquesM Patricia George
Department of Medicine, University of Pittsburgh, Pennsylvania 15213, USA
AIDS Res Hum Retroviruses 27:103-11. 2011..This SHIV-env model provides a new means to investigate HIV-PAH... - Nitrite in pulmonary arterial hypertension: therapeutic avenues in the setting of dysregulated arginine/nitric oxide synthase signallingBrian S Zuckerbraun
Department of Surgery, University of Pittsburgh, NW 607 MUH, 3459 Fifth Avenue, Pittsburgh, PA 15213, USA
Cardiovasc Res 89:542-52. 2011.... - Hemoglobin and the paracrine and endocrine functions of nitric oxideAlan N Schechter
National Institute of Diabetes and Digestive and Kidney Diseases, and the Critical Care Medicine Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892-1822, USA
N Engl J Med 348:1483-5. 2003 - Nitric oxide's reactions with hemoglobin: a view through the SNO-stormMark T Gladwin
Critical Care Medicine Department of the Warren G. Magnuson Clinical Center, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
Nat Med 9:496-500. 2003 - Emerging role of nitrite in human biologyAndre Dejam
Laboratory of Chemical Biology, National Institute of Diabetes, Digestive and Kidney Disease, National Institute of Health, Bethesda, MD 20892, USA
Blood Cells Mol Dis 32:423-9. 2004..This review focuses on the role of nitrite as a circulating NO donor, its potential as an index of NO synthase (NOS) activity and endothelial function, and discusses potential diagnostic and therapeutic applications... - Nitric oxide donor properties of hydroxyurea in patients with sickle cell diseaseMark T Gladwin
Critical Care Medicine Department of the Warren G Magnuson Clinical Center, Bethesda, MD 20892 1662, USA
Br J Haematol 116:436-44. 2002..The role of NO in the induction of fetal haemoglobin and possible synergy between NO donor therapy and classic cytostatic and differentiating medications should be explored... - NO solutions?Alan N Schechter
Laboratory of Chemical Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892, USA
J Clin Invest 109:1149-51. 2002 - Haldane, hot dogs, halitosis, and hypoxic vasodilation: the emerging biology of the nitrite anionMark T Gladwin
Critical Care Medicine Department, Warren G Magnuson Clinical Center, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 1662, USA
J Clin Invest 113:19-21. 2004..Nitrite levels in blood reflect NO production from endothelial NO synthase enzymes, and recent data suggest that nitrite contributes to blood flow regulation by reaction with deoxygenated hemoglobin and tissue heme proteins to form NO... - Measurement of circulating nitrite and S-nitrosothiols by reductive chemiluminescencePeter H MacArthur
Vascular Medicine Branch, National Heart Lung Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Chromatogr B Analyt Technol Biomed Life Sci 851:93-105. 2007..The underlying reaction mechanisms, as well as the potential pitfalls of each method are discussed... - Deconstructing endothelial dysfunction: soluble guanylyl cyclase oxidation and the NO resistance syndromeMark T Gladwin
Vascular Medicine Branch, National Heart, Lung, and Blood Institute, and Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA
J Clin Invest 116:2330-2. 2006..Diseases associated with NO resistance would appear to be ideally suited for therapies directed at restoring redox homeostasis, sGC activity, and NO sensitivity... - Hydroxyurea induces fetal hemoglobin by the nitric oxide-dependent activation of soluble guanylyl cyclaseVladan P Cokic
Laboratory of Chemical Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
J Clin Invest 111:231-9. 2003..These data provide strong evidence for an NO-derived mechanism for HbF induction by hydroxyurea and suggest possibilities for therapies based on NO-releasing or -potentiating agents... - Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell diseaseMaria L Jison
Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA
Blood 104:270-80. 2004..Global transcriptional analysis of circulating leukocytes highlights the intense oxidant and inflammatory nature of steady-state sickle cell disease and provides insight into the broad compensatory responses to vascular injury... - Methodological vexation about thiol oxidation versus S-nitrosation -- a commentary on "An ascorbate-dependent artifact that interferes with the interpretation of the biotin-switch assay"Mark T Gladwin
Vascular Medicine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Free Radic Biol Med 41:557-61. 2006 - A pharmacogenomic study of atorvastatin effects on eNOS activity: do "statins" modulate blood nitrite levels and intravascular oxidant stress in susceptible individuals?Cameron Dezfulian
Vascular Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA
Free Radic Biol Med 41:1041-3. 2006 - The measurement of blood and plasma nitrite by chemiluminescence: pitfalls and solutionsMildred M Pelletier
Molecular Medicine Branch, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA
Free Radic Biol Med 41:541-8. 2006....
Research Grants
- Myoglobin as a Nitrite Reductase that Regulates Hypoxic Cardiac NO SignalingSruti Shiva; Fiscal Year: 2010..This project will investigate how nitrite and myoglobin work together so that nitrite can be used to protect the heart during a heart attack. ..
- Storage Lesion in Banked Blood Due to Disruption of Nitric Oxide HomeostasisDaniel B Kim Shapiro; Fiscal Year: 2010..The project investigates the cause of this reduction in nitric oxide bioavailability and explores ways to restore nitric oxide upon red cell transfusion. ..