Stephen Black

Summary

Affiliation: Medical College of Georgia
Country: USA

Publications

  1. ncbi request reprint Pediatric pulmonary hypertension: Roles of endothelin-1 and nitric oxide
    Stephen M Black
    Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912, USA
    Clin Hemorheol Microcirc 37:111-20. 2007
  2. pmc Modulation of PKCdelta signaling alters the shear stress-mediated increases in endothelial nitric oxide synthase transcription: role of STAT3
    Neetu Sud
    Vascular Biology Center, Medical College of Georgia, Augusta, Georgia 30912, USA
    Am J Physiol Lung Cell Mol Physiol 296:L519-26. 2009
  3. pmc Endothelin-1 impairs nitric oxide signaling in endothelial cells through a protein kinase Cdelta-dependent activation of STAT3 and decreased endothelial nitric oxide synthase expression
    Neetu Sud
    Program in Pulmonary Vascular Disease, Vascular Biology Center, Medical College of Georgia, Augusta, Georgia 30912, USA
    DNA Cell Biol 28:543-53. 2009
  4. pmc Shear stress stimulates nitric oxide signaling in pulmonary arterial endothelial cells via a reduction in catalase activity: role of protein kinase C delta
    Sanjiv Kumar
    Vascular Biology Center CB 3210B, Medical College of Georgia, 1459 Laney Walker Blvd, Augusta, GA 30912, USA
    Am J Physiol Lung Cell Mol Physiol 298:L105-16. 2010
  5. doi request reprint Protein kinase Cdelta regulates endothelial nitric oxide synthase expression via Akt activation and nitric oxide generation
    Neetu Sud
    Vascular Biology Center, Medical College of Georgia, 1459 Laney Walker Blvd, CB 3210B, Augusta, GA 30912, USA
    Am J Physiol Lung Cell Mol Physiol 294:L582-91. 2008
  6. pmc The lectin-like domain of TNF protects from listeriolysin-induced hyperpermeability in human pulmonary microvascular endothelial cells - a crucial role for protein kinase C-alpha inhibition
    Chenling Xiong
    Medical College of Georgia, Augusta, GA, USA
    Vascul Pharmacol 52:207-13. 2010
  7. doi request reprint Harvesting, identification and barrier function of human lung microvascular endothelial cells
    John D Catravas
    Medical College of Georgia, Augusta, GA 30912 2300, USA
    Vascul Pharmacol 52:175-81. 2010
  8. ncbi request reprint Regulation of fibroblast growth factor-2 expression in pulmonary arterial smooth muscle cells involves increased reactive oxygen species generation
    Stephen M Black
    Vascular Biology Center, Medical College of Georgia, Augusta, Georgia, USA
    Am J Physiol Cell Physiol 294:C345-54. 2008
  9. ncbi request reprint Nitric oxide and superoxide generation from endothelial NOS: modulation by HSP90
    Neetu Sud
    Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912, USA
    Am J Physiol Lung Cell Mol Physiol 293:L1444-53. 2007
  10. doi request reprint Regulators of endothelial and epithelial barrier integrity and function in acute lung injury
    Rudolf Lucas
    Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912 2500, USA
    Biochem Pharmacol 77:1763-72. 2009

Research Grants

  1. Perinatal regulation of endothelial NOS
    Stephen M Black; Fiscal Year: 2010
  2. Perinatal regulation of TGF-beta1 during vascular remodeling
    Stephen Black; Fiscal Year: 2007
  3. Role of Neuronal NOS in Neurotoxicity
    Stephen Black; Fiscal Year: 2007
  4. Reactive Oxygen Species in PPHN
    Stephen Black; Fiscal Year: 2005
  5. ENOS Dimer Disruption and Endothelial Dysfunction
    Stephen Black; Fiscal Year: 2006
  6. NO-mediated signaling in endothelial cells
    Stephen Black; Fiscal Year: 2006
  7. Perinatal regulation of endothelial NOS
    Stephen Black; Fiscal Year: 2007
  8. Role of Neuronal NOS in Neurotoxicity
    Stephen M Black; Fiscal Year: 2010
  9. Perinatal regulation of TGF-beta1 during vascular remodeling
    Stephen M Black; Fiscal Year: 2010
  10. ROS in Pulmonary Hypertension: Role of ADMA
    Stephen M Black; Fiscal Year: 2010

Collaborators

Detail Information

Publications71

  1. ncbi request reprint Pediatric pulmonary hypertension: Roles of endothelin-1 and nitric oxide
    Stephen M Black
    Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912, USA
    Clin Hemorheol Microcirc 37:111-20. 2007
    ..In addition, we will suggest avenues of both basic and clinical research that will be important to develop novel pulmonary hypertension treatment and prevention strategies...
  2. pmc Modulation of PKCdelta signaling alters the shear stress-mediated increases in endothelial nitric oxide synthase transcription: role of STAT3
    Neetu Sud
    Vascular Biology Center, Medical College of Georgia, Augusta, Georgia 30912, USA
    Am J Physiol Lung Cell Mol Physiol 296:L519-26. 2009
    ..In conclusion, shear decreases PKCdelta activity and, subsequently, reduces STAT3 binding to the eNOS promoter. This signaling pathway plays a previously unidentified role in the regulation of eNOS expression by shear stress...
  3. pmc Endothelin-1 impairs nitric oxide signaling in endothelial cells through a protein kinase Cdelta-dependent activation of STAT3 and decreased endothelial nitric oxide synthase expression
    Neetu Sud
    Program in Pulmonary Vascular Disease, Vascular Biology Center, Medical College of Georgia, Augusta, Georgia 30912, USA
    DNA Cell Biol 28:543-53. 2009
    ..This in turn decreases eNOS promoter activity, protein levels, and NO production. Thus, ET-1 can reduce eNOS expression and NO generation in fetal pulmonary artery endothelial cells through PKCdelta-mediated activation of STAT3...
  4. pmc Shear stress stimulates nitric oxide signaling in pulmonary arterial endothelial cells via a reduction in catalase activity: role of protein kinase C delta
    Sanjiv Kumar
    Vascular Biology Center CB 3210B, Medical College of Georgia, 1459 Laney Walker Blvd, Augusta, GA 30912, USA
    Am J Physiol Lung Cell Mol Physiol 298:L105-16. 2010
    ....
  5. doi request reprint Protein kinase Cdelta regulates endothelial nitric oxide synthase expression via Akt activation and nitric oxide generation
    Neetu Sud
    Vascular Biology Center, Medical College of Georgia, 1459 Laney Walker Blvd, CB 3210B, Augusta, GA 30912, USA
    Am J Physiol Lung Cell Mol Physiol 294:L582-91. 2008
    ..ETU significantly inhibited NO production, eNOS promoter activity, and eNOS protein levels. Together, our data indicate involvement of PKCdelta-mediated Akt activation and NO generation in maintaining eNOS expression...
  6. pmc The lectin-like domain of TNF protects from listeriolysin-induced hyperpermeability in human pulmonary microvascular endothelial cells - a crucial role for protein kinase C-alpha inhibition
    Chenling Xiong
    Medical College of Georgia, Augusta, GA, USA
    Vascul Pharmacol 52:207-13. 2010
    ..These results indicate that the lectin-like domain of TNF has a potential therapeutic value in protecting from LLO-induced pulmonary endothelial hyperpermeability...
  7. doi request reprint Harvesting, identification and barrier function of human lung microvascular endothelial cells
    John D Catravas
    Medical College of Georgia, Augusta, GA 30912 2300, USA
    Vascul Pharmacol 52:175-81. 2010
    ..These HLMVEC present an in-house-derived alternative to commercially available human cells for the study of mechanisms contributing to ALI and ARDS...
  8. ncbi request reprint Regulation of fibroblast growth factor-2 expression in pulmonary arterial smooth muscle cells involves increased reactive oxygen species generation
    Stephen M Black
    Vascular Biology Center, Medical College of Georgia, Augusta, Georgia, USA
    Am J Physiol Cell Physiol 294:C345-54. 2008
    ..This positive feedback mechanism may contribute to pulmonary vascular remodeling associated with increased pulmonary blood flow...
  9. ncbi request reprint Nitric oxide and superoxide generation from endothelial NOS: modulation by HSP90
    Neetu Sud
    Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912, USA
    Am J Physiol Lung Cell Mol Physiol 293:L1444-53. 2007
    ....
  10. doi request reprint Regulators of endothelial and epithelial barrier integrity and function in acute lung injury
    Rudolf Lucas
    Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912 2500, USA
    Biochem Pharmacol 77:1763-72. 2009
    ..Unraveling the mechanism of action of these agents could contribute to the development of novel therapeutic strategies to combat permeability edema...
  11. doi request reprint Asymmetric dimethylarginine inhibits HSP90 activity in pulmonary arterial endothelial cells: role of mitochondrial dysfunction
    Neetu Sud
    Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912, USA
    Am J Physiol Cell Physiol 294:C1407-18. 2008
    ..Mitochondrial dysfunction may be an understudied component of the endothelial dysfunction associated with various cardiovascular disease states...
  12. ncbi request reprint Alterations in zinc homeostasis underlie endothelial cell death induced by oxidative stress from acute exposure to hydrogen peroxide
    Dean A Wiseman
    Vascular Biology Center, Medical College of Georgia, 1459 Laney Walker Blvd, Augusta, GA 30912, USA
    Am J Physiol Lung Cell Mol Physiol 292:L165-77. 2007
    ..We speculate that regulation of Zn(2+) levels may represent a potential therapeutic target for cardiovascular disease associated with acute oxidative stress...
  13. pmc Alterations in lung arginine metabolism in lambs with pulmonary hypertension associated with increased pulmonary blood flow
    Shruti Sharma
    Vascular Biology Center, 1459 Laney Walker Boulevard, CB3201B, Medical College of Georgia, Augusta, GA 30912, USA
    Vascul Pharmacol 51:359-64. 2009
    ....
  14. pmc Effect of PPARgamma inhibition on pulmonary endothelial cell gene expression: gene profiling in pulmonary hypertension
    Jing Tian
    Pulmonary Vascular Disease Program, Vascular Biology Center, Medical College of Georgia, Augusta, Georgia 30912, USA
    Physiol Genomics 40:48-60. 2009
    ..In conclusion, we have identified an array of endothelial genes modulated by attenuated PPARgamma signaling that may play important roles in the development of PH...
  15. ncbi request reprint Altered carnitine homeostasis is associated with decreased mitochondrial function and altered nitric oxide signaling in lambs with pulmonary hypertension
    Shruti Sharma
    Program in Pulmonary Disease, Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912, USA
    Am J Physiol Lung Cell Mol Physiol 294:L46-56. 2008
    ..Our data suggest that mitochondrial dysfunction may play a role in the development of endothelial dysfunction and pulmonary hypertension and increased pulmonary blood flow...
  16. doi request reprint Molecular mechanisms involved in adenosine-induced endothelial cell barrier enhancement
    Nagavedi S Umapathy
    Medical College of Georgia, Augusta, GA 30912, USA
    Vascul Pharmacol 52:199-206. 2010
    ..Our results suggest, for the first time, that adenosine regulates the EC barrier function via A2A receptors followed by Galphas engagement and is associated with cytoskeletal activation...
  17. pmc Inhibition of endothelial nitric oxide synthase by the lipid phosphatase PTEN
    Jarrod E Church
    Medical College of Georgia, Augusta, Georgia 30912, USA
    Vascul Pharmacol 52:191-8. 2010
    ..We conclude that PTEN is a regulator of eNOS function both when expressed in COS-7 cells and in human endothelial cells, and does so via its effects on the PI3K/Akt pathway...
  18. pmc Mass spectroscopy and molecular modeling predict endothelial nitric oxide synthase dimer collapse by hydrogen peroxide through zinc tetrathiolate metal-binding site disruption
    Fabio V Fonseca
    Vascular Biology Center, Medical College of Georgia, Augusta, 30912, USA
    DNA Cell Biol 29:149-60. 2010
    ..This study links the inhibitory action of H(2)O(2) on heNOS through the destruction of zinc tetrathiolate metal-binding site and dimer collapse both in vitro and in vivo...
  19. ncbi request reprint Nordihydroguaiaretic acid increases endothelial nitric oxide synthase expression via the transcription factor AP-1
    Sanjiv Kumar
    Vascular Biology Center, Medical College of Georgia, Augusta, Georgia 30912, USA
    DNA Cell Biol 26:853-62. 2007
    ....
  20. pmc Progressive dysfunction of nitric oxide synthase in a lamb model of chronically increased pulmonary blood flow: a role for oxidative stress
    Peter E Oishi
    Vascular Biology Center, Medical College of Georgia, 1459 Laney Walker Blvd, Augusta, GA 30912, USA
    Am J Physiol Lung Cell Mol Physiol 295:L756-66. 2008
    ..05). We conclude that increased pulmonary blood flow results in progressive impairment of basal and agonist-induced NOS function, in part secondary to oxidative stress that decreases bioavailable NO...
  21. doi request reprint Perinatal changes in superoxide generation in the ovine lung: Alterations associated with increased pulmonary blood flow
    Shruti Sharma
    Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912, United States
    Vascul Pharmacol 53:38-52. 2010
    ..Collectively, our findings suggest that NADPH oxidase and XO are major contributors to superoxide generation both during the normal development and during the development of pulmonary hypertension...
  22. pmc Estradiol increases guanosine 5'-triphosphate cyclohydrolase expression via the nitric oxide-mediated activation of cyclic adenosine 5'-monophosphate response element binding protein
    Xutong Sun
    Program in Pulmonary Vascular Disease, Vascular Biology Center, Medical College of Georgia, Augusta, Georgia 30912, USA
    Endocrinology 150:3742-52. 2009
    ..These findings provide new insight into the vascular protective effect of estradiol...
  23. pmc Caveolin 1 is required for the activation of endothelial nitric oxide synthase in response to 17beta-estradiol
    Neetu Sud
    Pulmonary Vascular Disease Program, Vascular Biology Center, Medical College of Georgia, Augusta, Georgia 30912, USA
    Mol Endocrinol 24:1637-49. 2010
    ..In conclusion, caveolin 1 stimulates 17beta-estradiol-induced NO production by promoting ERalpha to the plasma membrane, which facilitates the activation of the PI3 kinase pathway, leading to eNOS activation and NO generation...
  24. pmc Peroxynitrite mediates testosterone-induced vasodilation of microvascular resistance vessels
    Yashoda Puttabyatappa
    Department of Pharmacology and Toxicology, Georgia Health Sciences University, Augusta, Georgia, USA
    J Pharmacol Exp Ther 345:7-14. 2013
    ..We propose this mechanism could account for TES-stimulated cGMP production in microvessels and, ultimately, vasodilation...
  25. ncbi request reprint Lung antioxidant enzymes are regulated by development and increased pulmonary blood flow
    Shruti Sharma
    Vascular Biology Center, Medical College of Georgia, CB3210B, 1459 Laney Walker Blvd, Augusta, GA 30912, USA
    Am J Physiol Lung Cell Mol Physiol 293:L960-71. 2007
    ..An increased understanding of these alterations may have important therapeutic implications for the treatment of pulmonary hypertension secondary to increased pulmonary blood flow...
  26. pmc Deletion of protein tyrosine phosphatase 1b improves peripheral insulin resistance and vascular function in obese, leptin-resistant mice via reduced oxidant tone
    M Irfan Ali
    Vascular Biology Center, Medical College of Georgia, 1459 Laney Walker Blvd, Augusta, GA 30912, USA
    Circ Res 105:1013-22. 2009
    ..Insulin resistance is a common pathology in obese patients and has been shown to impair vascular function. Whether insulin resistance or obesity, itself, is causal remains unclear...
  27. pmc Hydrogen peroxide decreases endothelial nitric oxide synthase promoter activity through the inhibition of AP-1 activity
    Sanjiv Kumar
    Vascular Biology Center, Medical College of Georgia, 1459 Laney Walker Blvd, CB 3210 B, Augusta, GA 30912, USA
    Am J Physiol Lung Cell Mol Physiol 295:L370-7. 2008
    ..These data suggest a role of decreased AP-1 binding likely through c-Jun in the H(2)O(2)-mediated decrease in eNOS promoter activity...
  28. pmc Endothelial nitric oxide (NO) and its pathophysiologic regulation
    Anuran Chatterjee
    Pulmonary Vascular Disease Program, Vascular Biology Center, Medical College of Georgia, Augusta, Georgia 30912 2500, USA
    Vascul Pharmacol 49:134-40. 2008
    ....
  29. pmc Hydrogen peroxide decreases endothelial nitric oxide synthase promoter activity through the inhibition of Sp1 activity
    Sanjiv Kumar
    Vascular Biology Center, Medical College of Georgia, Augusta, Georgia 30912, USA
    DNA Cell Biol 28:119-29. 2009
    ..Together, these data suggest that the inhibition of Sp1 activity, possibly through loss of zinc in the protein, plays a role in the H(2)O(2)-induced inhibition of eNOS promoter activity...
  30. pmc GTP cyclohydrolase I expression is regulated by nitric oxide: role of cyclic AMP
    Sanjiv Kumar
    Vascular Biology Center, Medical College of Georgia, Augusta, 30912, USA
    Am J Physiol Lung Cell Mol Physiol 297:L309-17. 2009
    ..These data suggest that NO increases BH(4) levels through a cAMP/CREB-mediated increase in GCH1 transcription and that the eNOS uncoupling associated with exogenous NO does not involved reduced BH(4) levels...
  31. pmc Elevated zinc induces endothelial apoptosis via disruption of glutathione metabolism: role of the ADP translocator
    Dean A Wiseman
    Vascular Biology Center, Medical College of Georgia, 1459 Laney Walker Blvd CB 3210, Augusta, GA 30912 2500, USA
    Biometals 23:19-30. 2010
    ..These pathways could represent novel therapeutic targets during acute oxidative or nitrosative stress in cells and tissues...
  32. pmc Mechanisms of nitric oxide synthase uncoupling in endotoxin-induced acute lung injury: role of asymmetric dimethylarginine
    Shruti Sharma
    Medical College of Georgia, Augusta, GA 30912, USA
    Vascul Pharmacol 52:182-90. 2010
    ..In conclusion, this is the first study that suggests a role of the ADMA/DDAH pathway during the development of ALI in mice and that ADMA may be a novel therapeutic biomarker to ascertain the risk for development of ALI...
  33. ncbi request reprint Oxidative and nitrosative stress in pediatric pulmonary hypertension: roles of endothelin-1 and nitric oxide
    Stephen M Black
    Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT, United States
    Vascul Pharmacol 45:308-16. 2006
    ....
  34. ncbi request reprint Nitric oxide activates p21ras and leads to the inhibition of endothelial NO synthase by protein nitration
    Lisa A Brennan
    Department of Pediatrics, Northwestern University, Chicago, Illinois 60611 3008, USA
    DNA Cell Biol 22:317-28. 2003
    ..Our results implicate a signaling pathway involving p21ras activation, superoxide generation, and peroxynitrite formation as being important in the NO-mediated inhibition of eNOS...
  35. ncbi request reprint Role of reactive oxygen species in vascular remodeling associated with pulmonary hypertension
    Stephen Wedgwood
    Department of Pediatrics, Northwestern University, Chicago, IL 60611, USA
    Antioxid Redox Signal 5:759-69. 2003
    ..This review discusses the potential roles for ROS in the abnormal pulmonary vascular development characteristic of PPHN, and the treatment strategies arising from our increasing knowledge of the molecular mechanisms involved...
  36. ncbi request reprint Inhaled nitric oxide induced NOS inhibition and rebound pulmonary hypertension: a role for superoxide and peroxynitrite in the intact lamb
    Peter Oishi
    Department of Pediatrics, UC San Francisco, 505 Parnassus Ave, Box 0106, San Francisco, CA 94143 0106, USA
    Am J Physiol Lung Cell Mol Physiol 290:L359-66. 2006
    ..Reactive oxygen species scavenging may be a useful therapeutic strategy to ameliorate alterations in endogenous NO signaling during inhaled NO therapy...
  37. ncbi request reprint Nitric oxide decreases endothelin-1 secretion through the activation of soluble guanylate cyclase
    Lisa K Kelly
    International Heart Institute of Montana, St Patrick Hospital, 554 W Broadway, Missoula, MT 59802, USA
    Am J Physiol Lung Cell Mol Physiol 286:L984-91. 2004
    ..Therefore, we conclude that exposure of 4-wk PAECs to exogenous NO decreases secreted ET-1 resulting from the activation of sGC and increased cGMP generation...
  38. ncbi request reprint Endothelial alterations during inhaled NO in lambs with pulmonary hypertension: implications for rebound hypertension
    Gregory A Ross
    Department of Pediatrics, University of California, San Francisco, USA
    Am J Physiol Lung Cell Mol Physiol 288:L27-35. 2005
    ..These data suggest that the endothelial response to iNO and the potential mechanisms of rebound pulmonary hypertension are dependent upon the underlying pulmonary vasculature...
  39. ncbi request reprint Chronic endothelin A receptor blockade in lambs with increased pulmonary blood flow and pressure
    Sohrab Fratz
    Dept of Pediatric Cardiology and Congenital Heart Disease, Deutsches Herzzentrum Munchen, Klinik an der Technischen Universit√§t M√ľnchen, Lazarettstr 36, 80636 Munich, Germany
    Am J Physiol Lung Cell Mol Physiol 287:L592-7. 2004
    ..We conclude that chronic endothelin A receptor blockade attenuates the progression of pulmonary hypertension and augments alveolar growth in lambs with increased pulmonary blood flow...
  40. ncbi request reprint Alterations in ET-1, not nitric oxide, in 1-week-old lambs with increased pulmonary blood flow
    Boaz Ovadia
    Department of Pediatrics, University of California, San Francisco, 94143, USA
    Am J Physiol Heart Circ Physiol 284:H480-90. 2003
    ..These data demonstrate that increased pulmonary blood flow induces alterations in ET-1 signaling before NO signaling and suggest an early role for ET-1 in the altered vascular reactivity associated with increased pulmonary blood flow...
  41. ncbi request reprint p21ras activation following hypoxia-ischemia in the newborn rat brain is dependent on nitric oxide synthase activity but p21ras does not contribute to neurologic injury
    Mark S Wainwright
    Department of Pediatrics, Division of Neurology, Northwestern University, Chicago, IL, USA
    Brain Res Dev Brain Res 146:79-85. 2003
    ..Ras does not, however, contribute to the pathophysiologic NO-dependent mechanisms of neurologic injury in this model...
  42. ncbi request reprint Combined superoxide dismutase/catalase mimetics alter fetal pulmonary arterial smooth muscle cell growth
    Stephen Wedgwood
    Department of Pediatrics, Northwestern University Medical School, Chicago, IL 60611 3008, USA
    Antioxid Redox Signal 6:191-7. 2004
    ..Titration of ROS with antioxidants may help to prevent, or reverse, the vascular remodeling manifest in many cardiovascular disease states...
  43. ncbi request reprint Emergence of smooth muscle cell endothelin B-mediated vasoconstriction in lambs with experimental congenital heart disease and increased pulmonary blood flow
    Stephen M Black
    Department of Pediatrics, Northwestern University, Chicago, Ill, USA
    Circulation 108:1646-54. 2003
    ..The objective of this study was to investigate the role of potential later alterations of the ET cascade in the pathophysiology of pulmonary hypertension secondary to increased pulmonary blood flow...
  44. ncbi request reprint Endothelial response to stress from exogenous Zn2+ resembles that of NO-mediated nitrosative stress, and is protected by MT-1 overexpression
    Dean A Wiseman
    International Heart Institute, St Patrick Hospital, 554 W Broadway, Missoula, MT 59802, USA
    Am J Physiol Cell Physiol 291:C555-68. 2006
    ..We propose that regulation of Zn(2+) levels may represent a potential therapeutic target for disease associated with both nitrosative and oxidative stress...
  45. ncbi request reprint Expression of VEGF and its receptors Flt-1 and Flk-1/KDR is altered in lambs with increased pulmonary blood flow and pulmonary hypertension
    Eugenia Mata-Greenwood
    Department of Pediatrics, Northwestern University, Chicago, Illinois 60611 3008, USA
    Am J Physiol Lung Cell Mol Physiol 285:L222-31. 2003
    ..Our data suggest that increased pulmonary blood flow upregulates expression of VEGF and its receptors, and this may be important in development of the vascular remodeling in shunted lambs...
  46. ncbi request reprint Induction of apoptosis in fetal pulmonary arterial smooth muscle cells by a combined superoxide dismutase/catalase mimetic
    Stephen Wedgwood
    Department of Pediatrics, Northwestern University Medical School, Chicago, IL 60611 3008, USA
    Am J Physiol Lung Cell Mol Physiol 285:L305-12. 2003
    ..Compounds such as EUK-134 may, therefore, prove more effective than enzymic antioxidants over longer periods, especially when the aim is to decrease the number of smooth muscle cells in diseases resulting from excessive muscularization...
  47. ncbi request reprint Alterations in TGF-beta1 expression in lambs with increased pulmonary blood flow and pulmonary hypertension
    Eugenia Mata-Greenwood
    Department of Pediatrics, Northwestern University, Chicago, Illinois 60611 3008, USA
    Am J Physiol Lung Cell Mol Physiol 285:L209-21. 2003
    ..Our data suggest that increased pulmonary blood flow dysregulates TGF-beta1 signaling, producing imbalance between pro- and antiangiogenic signaling that may be important in vascular remodeling in shunted lambs...
  48. ncbi request reprint Developmental changes in murine brain antioxidant enzymes
    Janine Y Khan
    Department of Pediatrics and Molecular Pharmacology, Northwestern University, Chicago, IL 60611, USA
    Pediatr Res 54:77-82. 2003
    ..These data will be important in our future understanding of the mechanisms by which hypoxia mediates injury in the immature and the mature brain...
  49. ncbi request reprint The overexpression catalase reduces NO-mediated inhibition of endothelial NO synthase
    Lisa A Brennan
    Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois 60611 3008, USA
    IUBMB Life 54:261-5. 2002
    ....
  50. ncbi request reprint Developmental differences in the shear stress-induced expression of endothelial NO synthase: changing role of AP-1
    Stephen Wedgwood
    Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois 60611 3008, USA
    Am J Physiol Lung Cell Mol Physiol 284:L650-62. 2003
    ..We have therefore identified mechanisms of eNOS regulation at the transcriptional level and to be enzyme activation specific to the fetal pulmonary arterial circulation...
  51. ncbi request reprint The overexpression of copper-zinc superoxide dismutase protects NOS III from nitric oxide-mediated inhibition
    Lisa A Brennan
    Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois, USA
    DNA Cell Biol 21:827-38. 2002
    ....
  52. ncbi request reprint Alterations in nitric oxide production in 8-week-old lambs with increased pulmonary blood flow
    Stephen M Black
    Department of Pediatrics, Northwestern University, Chicago, Illinois, USA
    Pediatr Res 52:233-44. 2002
    ..We speculate that the progressive decrease in basal NO activity participates in the development of pulmonary hypertension secondary to increased pulmonary blood flow...
  53. pmc S-nitrosylation of endothelial nitric oxide synthase is associated with monomerization and decreased enzyme activity
    Kandasam Ravi
    Department of Pediatrics, Northwestern University, Chicago, IL 60611 3008, USA
    Proc Natl Acad Sci U S A 101:2619-24. 2004
    ..Therefore, this study links the inhibitory action of NO with the destruction of zinc tetrathiolate cluster at the dimeric interface through S-nitrosylation of the cysteine residues...
  54. ncbi request reprint Molecular mechanisms of nitric oxide-induced growth arrest and apoptosis in fetal pulmonary arterial smooth muscle cells
    Stephen Wedgwood
    Department of Pediatrics, Northwestern University Medical School, Chicago, IL 60611 3008, USA
    Nitric Oxide 9:201-10. 2003
    ..NO donors may therefore prove to be useful therapeutic tools to treat diseases resulting from excessive proliferation of vascular smooth muscle...
  55. ncbi request reprint Phosphodiesterase-3 inhibition prevents the increase in pulmonary vascular resistance following inhaled nitric oxide withdrawal in lambs
    Stephan Thelitz
    Department of Cardiothoracic Surgery, University of California, San Francisco, CA, USA
    Pediatr Crit Care Med 5:234-9. 2004
    ....
  56. ncbi request reprint Increased oxidative stress in lambs with increased pulmonary blood flow and pulmonary hypertension: role of NADPH oxidase and endothelial NO synthase
    Albert C Grobe
    Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59802, USA
    Am J Physiol Lung Cell Mol Physiol 290:L1069-77. 2006
    ..Rather, the observed increase in oxidative stress is due, at least in part, to increased expression and activity of the NADPH oxidase complex and uncoupled eNOS due to elevated levels of BH(2)...
  57. ncbi request reprint Nitric oxide-endothelin-1 interactions after surgically induced acute increases in pulmonary blood flow in intact lambs
    Peter Oishi
    Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143 0106, USA
    Am J Physiol Heart Circ Physiol 290:H1922-32. 2006
    ..Thus NO appears to be important in maintaining a reduction in PVR after acutely increased PBF...
  58. ncbi request reprint Vascular endothelium summary statement V: Pulmonary hypertension and acute lung injury: public health implications
    W Craig Hooper
    National Center for Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention CDC, Mailstop DO 2, 1600 Clifton Road, Atlanta, GA 30333, USA
    Vascul Pharmacol 46:327-9. 2007
    ..This summary statement briefly summarizes the state of the science and suggests future avenues of public health research...
  59. ncbi request reprint Fibroblast growth factor-2 expression is altered in lambs with increased pulmonary blood flow and pulmonary hypertension
    Stephen Wedgwood
    Department of Pediatrics, Northwestern University, Chicago, Illinois 60611, USA
    Pediatr Res 61:32-6. 2007
    ..Elevated FGF-2 signaling by PASMC and PAEC exposed to increased pulmonary blood flow may play a role in the pulmonary vascular remodeling associated with the shunt model of pulmonary hypertension secondary to congenital heart disease...
  60. pmc A nitric oxide donor reduces brain injury and enhances recovery of cerebral blood flow after hypoxia-ischemia in the newborn rat
    Mark S Wainwright
    Department of Pediatrics, Division of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60614, USA
    Neurosci Lett 415:124-9. 2007
    ..Augmentation of NO-dependent increases in CBF may serve to improve neurologic outcome after perinatal asphyxia...
  61. pmc The role of nitric oxide synthase-derived reactive oxygen species in the altered relaxation of pulmonary arteries from lambs with increased pulmonary blood flow
    Satyan Lakshminrusimha
    Department of Pediatrics, Women s and Children s Hospital of Buffalo, State University of New York at Buffalo, NY 14222, USA
    Am J Physiol Heart Circ Physiol 293:H1491-7. 2007
    ..The redox environment, influenced by the balance between production and scavenging of ROS, may have important consequences on pulmonary vascular reactivity in the setting of increased Q(p)...
  62. pmc eNOS function is developmentally regulated: uncoupling of eNOS occurs postnatally
    Eugenia Mata-Greenwood
    Dept of Pediatrics, Northwestern Univ, Ward 12 191, 303 E Chicago Ave, Chicago, IL 60611 008, USA
    Am J Physiol Lung Cell Mol Physiol 290:L232-41. 2006
    ..We speculate this may be related to cellular production and/or maintenance of BH4 levels...
  63. pmc Increased hydrogen peroxide downregulates soluble guanylate cyclase in the lungs of lambs with persistent pulmonary hypertension of the newborn
    Stephen Wedgwood
    Dept of Pediatrics, Northwestern University, Chicago, Illinois, USA
    Am J Physiol Lung Cell Mol Physiol 289:L660-6. 2005
    ..Overall our data suggest a role for H(2)O(2) in the abnormal vasodilation associated with the pulmonary arteries of PPHN lambs...
  64. ncbi request reprint Neuronal nitric oxide synthase activity in the paraventricular nucleus buffers central endothelin-1- induced pressor response and vasopressin secretion
    Noreen F Rossi
    Department of Medicine, Wayne State University School of Medicine and John D Dingell VA Medical Center, Detroit, Michigan 48201, USA
    J Cardiovasc Pharmacol 44:S283-8. 2004
    ....
  65. ncbi request reprint Cyclic stretch increases VEGF expression in pulmonary arterial smooth muscle cells via TGF-beta1 and reactive oxygen species: a requirement for NAD(P)H oxidase
    Eugenia Mata-Greenwood
    International Heart Institute of Montana, 3rd Floor, St Patrick Hospital, 554 West Broadway, Missoula, MT 59802, USA
    Am J Physiol Lung Cell Mol Physiol 289:L288-9. 2005
    ..Therefore, our results indicate that cyclic stretch upregulates VEGF expression via the TGF-beta1-dependent activation of NAD(P)H oxidase and increased generation of ROS...
  66. ncbi request reprint Endothelin-1 in congenital heart disease
    Maurice Beghetti
    Pediatric Cardiology Unit, Department of Pediatrics, Children s University Hospital, Geneva, Switzerland
    Pediatr Res 57:16R-20R. 2005
    ..In addition, therapeutic implications for the use of novel ET receptor antagonists will be emphasized...
  67. ncbi request reprint Inhibition of protein-tyrosine phosphatases by mild oxidative stresses is dependent on S-nitrosylation
    Daniel M Barrett
    Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia 23298 0058, USA
    J Biol Chem 280:14453-61. 2005
    ..These results support the conclusion that a mild oxidative signal is converted to a nitrosative one due to the better redox signaling properties of NO...
  68. ncbi request reprint Endothelin-1 decreases endothelial NOS expression and activity through ETA receptor-mediated generation of hydrogen peroxide
    Stephen Wedgwood
    Deparment of Pediatrics, Northwestern University, Chicago, Illinois, USA
    Am J Physiol Lung Cell Mol Physiol 288:L480-7. 2005
    ..These data suggest a role for smooth muscle cell-derived H2O2 in ET-1-mediated downregulation of eNOS expression in children born with PPHN...
  69. ncbi request reprint Important role for Rac1 in regulating reactive oxygen species generation and pulmonary arterial smooth muscle cell growth
    Sandip Patil
    Department of Pediatrics, Northwestern University, Chicago, Illinois 60611, USA
    Am J Physiol Lung Cell Mol Physiol 287:L1314-22. 2004
    ..These results indicate the importance of Rac1 in ROS generation and proliferation of vascular smooth muscle cells...
  70. ncbi request reprint Inhaled nitric oxide decreases pulmonary soluble guanylate cyclase protein levels in 1-month-old lambs
    Stephan Thelitz
    Department of Cardiothoracic Surgery, University of California, San Francisco 94143 0106, USA
    J Thorac Cardiovasc Surg 127:1285-92. 2004
    ..We sought to determine the effects of inhaled nitric oxide on endogenous cyclic guanosine monophosphate levels, soluble guanylate cyclase, and phosphodiesterase 5 protein levels in the intact lamb...
  71. ncbi request reprint Nitric oxide-endothelin-1 interactions after acute ductal constriction in fetal lambs
    Boaz Ovadia
    Department of Pediatrics, University of California, San Francisco, California 94143 0106, USA
    Am J Physiol Heart Circ Physiol 282:H862-71. 2002
    ..The mechanisms of these NO-ET-1 interactions, and their role in mediating acute changes in PBF, warrant further studies...

Research Grants43

  1. Perinatal regulation of endothelial NOS
    Stephen M Black; Fiscal Year: 2010
    ....
  2. Perinatal regulation of TGF-beta1 during vascular remodeling
    Stephen Black; Fiscal Year: 2007
    ..The information garnered from these studies will elucidate the mechanisms by which biomechanical forces regulate the TGF-b1/VEGF axis and should prove to be significant in developing new treatment strategies for children with CHD. ..
  3. Role of Neuronal NOS in Neurotoxicity
    Stephen Black; Fiscal Year: 2007
    ..It is anticipated that the data obtained will identify signaling intermediates that could be targeted to produce new therapeutic agents for infants and children exposed to asphxia. ..
  4. Reactive Oxygen Species in PPHN
    Stephen Black; Fiscal Year: 2005
    ..abstract_text> ..
  5. ENOS Dimer Disruption and Endothelial Dysfunction
    Stephen Black; Fiscal Year: 2006
    ..These include pulmonary and systemic hypertension, diabetes, and atherosclerosis. ..
  6. NO-mediated signaling in endothelial cells
    Stephen Black; Fiscal Year: 2006
    ..Clinically, these studies may be important in interventions directed at pathophysiological disorders in which redox signaling is involved. ..
  7. Perinatal regulation of endothelial NOS
    Stephen Black; Fiscal Year: 2007
    ..It is anticipated that the successful completion of these studies will increase our understanding of the role played by estrogen in regulating eNOS activity and expression in the pulmonary system in the perinatal period. ..
  8. Role of Neuronal NOS in Neurotoxicity
    Stephen M Black; Fiscal Year: 2010
    ..It is anticipated that the data obtained will identify signaling intermediates that could be targeted to produce new therapeutic agents for infants and children exposed to asphxia. ..
  9. Perinatal regulation of TGF-beta1 during vascular remodeling
    Stephen M Black; Fiscal Year: 2010
    ..The information garnered from these studies will elucidate the mechanisms by which biomechanical forces regulate the TGF-b1/VEGF axis and should prove to be significant in developing new treatment strategies for children with CHD. ..
  10. ROS in Pulmonary Hypertension: Role of ADMA
    Stephen M Black; Fiscal Year: 2010
    ....
  11. Role of Neuronal NOS in Neurotoxicity
    Stephen Black; Fiscal Year: 2009
    ..It is anticipated that the data obtained will identify signaling intermediates that could be targeted to produce new therapeutic agents for infants and children exposed to asphxia. ..
  12. Perinatal regulation of TGF-beta1 during vascular remodeling
    Stephen Black; Fiscal Year: 2009
    ..The information garnered from these studies will elucidate the mechanisms by which biomechanical forces regulate the TGF-b1/VEGF axis and should prove to be significant in developing new treatment strategies for children with CHD. ..
  13. ENOS Dimer Disruption and Endothelial Dysfunction
    Stephen Black; Fiscal Year: 2003
    ..These include pulmonary and systemic hypertension, diabetes, and atherosclerosis. ..
  14. THE ROLE OF NEURONAL NOS DIMERIZATION IN NEUROTOXICITY
    Stephen Black; Fiscal Year: 2002
    ..We will identify how these factors interact to regulate nNOS dimer formation and hence nNOS activity. ..
  15. PERINATAL REGULATION OF THE ENDOTHELIAL NOS GENE
    Stephen Black; Fiscal Year: 2001
    ..This may eventually lead to the identification of transcription (transacting) factors responsible for the increase in eNOS gene expression during the transition from fetal to neonatal life. ..
  16. NO-mediated signaling in endothelial cells
    Stephen Black; Fiscal Year: 2003
    ..Clinically, these studies may be important in interventions directed at pathophysiological disorders in which redox signaling is involved. ..