Interactions Between Inflammation, Oxidant Stress and Cardiovascular Disease

Summary

Principal Investigator: David G Harrison
Abstract: This is a continuing application of a successful program project that has focused on reactive oxygen species (ROS) and their role in cardiovascular disease. The present proposal combines talents of several outstanding investigators with a new emphasis on the interplay between inflammation and oxidant stress and the manner in which these contribute to hypertension, atherosclerotic plaque formation and response to disease. Project 1 will focus on a newly recognized role of the T cell in the genesis of hypertension and will seek to determine mechanisms responsible for T cell homing. Studies will determine if interruption of T cell entry into tissues prevents hypertension. Project 2 will delineate the respective roles of plasmacytoid and myeloid dendritic cells (DCs) and their upstream signals in plaque formation. In this project, signals which act on toll-like receptors will be used to selectively activate respective DC subtypes and the consequent T cell/macrophage recruitment and activation in intact plaques will be defined The role of DCs and T cells in promoting vascular smooth muscle death, NADPH oxidase expression and ROS production will be defined and a novel therapeutic approach to suppress tissue injury in the plaque will be examined. Project 3 has arisen from a very successful ongoing collaboration among the project investigators in which a phenomenon first observed in vascular biology studies was found to be responsible for diastolic dysfunction in hypertension. Preliminary data indicates that hypertension causes oxidation of the NO synthase co-factor tetrahydrobiopterin in the heart, and that this leads to uncoupling of nitric oxide synthase and diastolic dysfunction. Studies will be performed that will delineate the cell type involved in ROS production in the heart and novel therapeutic approaches will be employed, which if successful, would provide the first direct treatment of diastolic dysfunction. A mouse that develops cardiac oxidative stress and diastolic dysfunction without hypertension will allow us to separate the effects of blood pressure lowering versus recoupling of nitric oxide synthase in improvement of diastole function. Our PPG will be supported by two Cores that will provide expertise with detection of ROS and histological analysis of relevant tissues. Overall, these studies will promote our understanding of the interplay between inflammation, oxidant stress and cardiovascular disease.
Funding Period: 1999-05-01 - 2014-12-31
more information: NIH RePORT

Top Publications

  1. pmc EPR detection of cellular and mitochondrial superoxide using cyclic hydroxylamines
    Sergey I Dikalov
    FRIMCORE, Emory University School of Medicine, Atlanta, GA, USA
    Free Radic Res 45:417-30. 2011
  2. pmc Inhibition of c-Src tyrosine kinase prevents angiotensin II-mediated connexin-43 remodeling and sudden cardiac death
    Ali A Sovari
    Section of Cardiology and Center for Cardiovascular Research, University of Illinois at Chicago, 840 S Wood Street, Chicago, IL 60612, USA
    J Am Coll Cardiol 58:2332-9. 2011
  3. ncbi Mechanisms of immunosenescence: lessons from models of accelerated immune aging
    Sabine Le Saux
    Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California, USA
    Ann N Y Acad Sci 1247:69-82. 2012
  4. pmc Dampened ERK signaling in hematopoietic progenitor cells in rheumatoid arthritis
    Ines Colmegna
    Department of Medicine, Division of Immunology and Rheumatology, Stanford University, USA
    Clin Immunol 143:73-82. 2012
  5. pmc Ranolazine improves cardiac diastolic dysfunction through modulation of myofilament calcium sensitivity
    Joshua D Lovelock
    Section of Cardiology, University of Illinois at Chicago, 60612, USA
    Circ Res 110:841-50. 2012
  6. pmc Signal inhibition by the dual-specific phosphatase 4 impairs T cell-dependent B-cell responses with age
    Mingcan Yu
    Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
    Proc Natl Acad Sci U S A 109:E879-88. 2012
  7. pmc Mitochondrial reactive oxygen species and calcium uptake regulate activation of phagocytic NADPH oxidase
    Sergey I Dikalov
    Division of Clinical Pharmacology, Vanderbilt Medical Center, Nashville, Tennessee 37232 6602, USA
    Am J Physiol Regul Integr Comp Physiol 302:R1134-42. 2012
  8. pmc Chronic inflammation and aging: DNA damage tips the balance
    Mary M Cavanagh
    Department of Medicine, Stanford University, Stanford, CA 94305, United States
    Curr Opin Immunol 24:488-93. 2012
  9. pmc Determination of ebselen-sensitive reactive oxygen metabolites (ebROM) in human serum based upon N,N'-diethyl-1,4-phenylenediamine oxidation
    Yongliang Liang
    Clinical Biomarkers Laboratory, Allergy and Critical Care Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, United States
    Clin Chim Acta 414:1-6. 2012
  10. pmc Association of low plasma adiponectin with early diastolic dysfunction
    Smita I Negi
    Section of Cardiology, University of Illinois at Chicago, Chicago, IL 60612, USA
    Congest Heart Fail 18:187-91. 2012

Research Grants

Detail Information

Publications120 found, 100 shown here

  1. pmc EPR detection of cellular and mitochondrial superoxide using cyclic hydroxylamines
    Sergey I Dikalov
    FRIMCORE, Emory University School of Medicine, Atlanta, GA, USA
    Free Radic Res 45:417-30. 2011
    ..These data show that a new set of hydroxylamine spin probes provide unique information about site-specific production of the O₂ⁱ⁻ radical in extracellular or intracellular compartments, cytoplasm or mitochondria...
  2. pmc Inhibition of c-Src tyrosine kinase prevents angiotensin II-mediated connexin-43 remodeling and sudden cardiac death
    Ali A Sovari
    Section of Cardiology and Center for Cardiovascular Research, University of Illinois at Chicago, 840 S Wood Street, Chicago, IL 60612, USA
    J Am Coll Cardiol 58:2332-9. 2011
    ..The aim of this study was to test whether c-Src tyrosine kinase mediates connexin-43 (Cx43) reduction and sudden cardiac death in a transgenic mouse model of cardiac-restricted overexpression of angiotensin-converting enzyme (ACE8/8 mice)...
  3. ncbi Mechanisms of immunosenescence: lessons from models of accelerated immune aging
    Sabine Le Saux
    Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California, USA
    Ann N Y Acad Sci 1247:69-82. 2012
    ..Studies of accelerated immune aging in autoimmune diseases have identified an unexpected link to chronic DNA damage responses that are known to be important in aging, but so far had not been implicated in immune aging...
  4. pmc Dampened ERK signaling in hematopoietic progenitor cells in rheumatoid arthritis
    Ines Colmegna
    Department of Medicine, Division of Immunology and Rheumatology, Stanford University, USA
    Clin Immunol 143:73-82. 2012
    ..Thus, hyporesponsiveness of RA HPC to growth factors results from dampening of the ERK signaling pathways; with a defect localized in the very early steps of the ERK signaling cascade...
  5. pmc Ranolazine improves cardiac diastolic dysfunction through modulation of myofilament calcium sensitivity
    Joshua D Lovelock
    Section of Cardiology, University of Illinois at Chicago, 60612, USA
    Circ Res 110:841-50. 2012
    ..Oxidative stress has been shown to increase late inward sodium current (I(Na)), reducing the net cytosolic Ca(2+) efflux...
  6. pmc Signal inhibition by the dual-specific phosphatase 4 impairs T cell-dependent B-cell responses with age
    Mingcan Yu
    Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
    Proc Natl Acad Sci U S A 109:E879-88. 2012
    ..004) was restored. Our data suggest that increased DUSP4 expression in activated T cells in the elderly in part accounts for defective adaptive immune responses...
  7. pmc Mitochondrial reactive oxygen species and calcium uptake regulate activation of phagocytic NADPH oxidase
    Sergey I Dikalov
    Division of Clinical Pharmacology, Vanderbilt Medical Center, Nashville, Tennessee 37232 6602, USA
    Am J Physiol Regul Integr Comp Physiol 302:R1134-42. 2012
    ..In summary, increased mitochondrial O(2)(·-) and impaired buffering of cytosolic Ca(2+) by dysfunctional mitochondria result in enhanced NADPH oxidase activity, which may contribute to the development of cardiovascular diseases...
  8. pmc Chronic inflammation and aging: DNA damage tips the balance
    Mary M Cavanagh
    Department of Medicine, Stanford University, Stanford, CA 94305, United States
    Curr Opin Immunol 24:488-93. 2012
    ..When these lymphocytes are exposed to inflammatory signals produced by senescent tissues, the bias toward inflammation exacerbates destruction without necessarily improving immunity...
  9. pmc Determination of ebselen-sensitive reactive oxygen metabolites (ebROM) in human serum based upon N,N'-diethyl-1,4-phenylenediamine oxidation
    Yongliang Liang
    Clinical Biomarkers Laboratory, Allergy and Critical Care Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, United States
    Clin Chim Acta 414:1-6. 2012
    ..A convenient assay for oxidants in human serum is based upon the Fe(2+)-dependent decomposition of peroxides to oxidize N,N'-diethyl-1,4-phenylenediamine (DEPPD) to a stable radical cation which can be measured spectrophotometrically...
  10. pmc Association of low plasma adiponectin with early diastolic dysfunction
    Smita I Negi
    Section of Cardiology, University of Illinois at Chicago, Chicago, IL 60612, USA
    Congest Heart Fail 18:187-91. 2012
    ..02), HMW fraction (P=.03), and MMW+LMW fraction (P=.004) in similar linear regression analyses. Adiponectin deficiency may be one explanation for the adiposity-related cardiac oxidation known to be involved in the pathogenesis of DD...
  11. pmc CD8+CD45RA+CCR7+FOXP3+ T cells with immunosuppressive properties: a novel subset of inducible human regulatory T cells
    Masakatsu Suzuki
    Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
    J Immunol 189:2118-30. 2012
    ..Loss of CD8+CCR7+ Tregs in the elderly host may be of relevance in the aging immune system as immunosenescence is associated with a state of chronic smoldering inflammation...
  12. pmc Metabolic stress, reactive oxygen species, and arrhythmia
    Euy Myoung Jeong
    Section of Cardiology, University of Illinois at Chicago, Chicago, IL 60612, USA
    J Mol Cell Cardiol 52:454-63. 2012
    ..This article is part of a Special Issue entitled "Local Signaling in Myocytes"...
  13. pmc Role of RBM25/LUC7L3 in abnormal cardiac sodium channel splicing regulation in human heart failure
    Ge Gao
    Section of Cardiology, University of Illinois at Chicago, 840 S Wood St, MC 715, Chicago, IL 60612, USA
    Circulation 124:1124-31. 2011
    ..Splicing factor expression profiles during human heart failure and a specific splicing pathway for SCN5A regulation were explored in this study...
  14. pmc The central nervous system and inflammation in hypertension
    Paul J Marvar
    Divison of Cardiology, Department of Medicine, Emory University School of Medicine and the Atlanta Veteran Administration Hospital, Atlanta, GA, USA
    Curr Opin Pharmacol 11:156-61. 2011
    ..The neuro-immune system plays an essential role in the pathogenesis of hypertension and further understanding of this relationship could lead to the development of new treatment strategies...
  15. pmc Blocking the NOTCH pathway inhibits vascular inflammation in large-vessel vasculitis
    Kisha Piggott
    Lowance Center for Human Immunology and Rheumatology, Emory University, Atlanta, GA, USA
    Circulation 123:309-18. 2011
    ....
  16. pmc Role of interleukin 17 in inflammation, atherosclerosis, and vascular function in apolipoprotein e-deficient mice
    Meena S Madhur
    Division of Cardiology, Emory University, Atlanta, GA, USA
    Arterioscler Thromb Vasc Biol 31:1565-72. 2011
    ..Interleukin 17A (IL17A) is involved in many inflammatory processes, but its role in atherosclerosis remains controversial. We examined the role of IL17A in mouse and human atherosclerosis...
  17. pmc Tetrahydrobiopterin deficiency and nitric oxide synthase uncoupling contribute to atherosclerosis induced by disturbed flow
    Li Li
    Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
    Arterioscler Thromb Vasc Biol 31:1547-54. 2011
    ..We therefore aimed to determine whether atherosclerosis induced by disturbed flow is due to BH(4) deficiency and NOS uncoupling and whether increasing BH(4) would prevent endothelial dysfunction, plaque inflammation, and atherosclerosis...
  18. pmc Inhibition of renin-angiotensin system (RAS) reduces ventricular tachycardia risk by altering connexin43
    Shahriar Iravanian
    Division of Cardiology, Atlanta Veterans Affairs Medical Center and Emory University, GA, 30033, USA
    J Mol Med (Berl) 89:677-87. 2011
    ..50. In a model of RAS activation, arrhythmic risk was correlated with reduced Cx43 amount and phosphorylation. RAS inhibition resulted in increased total and phosphorylated Cx43, decreased VT inducibility, and improved survival...
  19. pmc Anti-inflammatory activity of Chios mastic gum is associated with inhibition of TNF-alpha induced oxidative stress
    Angelike Triantafyllou
    Medical School of Athens, Athens, Greece
    Nutr J 10:64. 2011
    ..The molecular mechanisms of its anti-inflammatory activity, however, are not clear. In this work, the potential role of antioxidant activity of Chios mastic gum has been evaluated...
  20. ncbi A novel high-throughput screening assay for discovery of molecules that increase cellular tetrahydrobiopterin
    Li Li
    The Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
    J Biomol Screen 16:836-44. 2011
    ..Thus, this TR-FRET assay could be applied in future uHTS of additional libraries to search for molecules that increase GTPCH-1 activity and BH(4) levels...
  21. pmc Diastolic dysfunction is associated with cardiac fibrosis in the senescence-accelerated mouse
    Alana L Reed
    Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine Atlanta Veterans Affairs Medical Center, Atlanta, Georgia 30033, USA
    Am J Physiol Heart Circ Physiol 301:H824-31. 2011
    ..05 for all data). In summary, SAMP8 mice show increased fibrosis and diastolic dysfunction similar to those seen in humans with aging and may represent a suitable model for future mechanistic studies...
  22. pmc Role of vascular extracellular superoxide dismutase in hypertension
    Heinrich E Lob
    Division of Clinical Pharmacology, 536 Robinson Research Building, Vanderbilt University School of Medicine, Nashville, TN 37232 6602, USA
    Hypertension 58:232-9. 2011
    ....
  23. pmc Cardiac autoantibodies from patients affected by a new variant of endemic pemphigus foliaceus in Colombia, South America
    Ana Maria Abreu-Velez
    Georgia Dermatopathology Associates, Atlanta, Georgia, USA
    J Clin Immunol 31:985-97. 2011
    ....
  24. pmc Use of human embryonic stem cell derived-mesenchymal cells for cardiac repair
    David L Simpson
    University of Illinois at Chicago Jesse Brown VA Medical Center, 840 S Wood Street, MC715, Chicago, Illinois 60612, USA
    Biotechnol Bioeng 109:274-83. 2012
    ..In summary, the use of hES-MC provides similar efficacy for cellular cardiomyoplasty as compared to hMSC and may be considered a suitable alternative for cell therapy...
  25. ncbi The immunopathology of giant cell arteritis: diagnostic and therapeutic implications
    Cornelia M Weyand
    Department of Medicine, and the Byers Eye Institute at Stanford, Stanford University, Stanford, CA, USA
    J Neuroophthalmol 32:259-65. 2012
    ..Expansion of the therapeutic armamentarium for GCA needs to focus on approaches that mitigate the impact of the aging artery and adapt to the needs of the immunosenescent host...
  26. pmc RBM25/LUC7L3 function in cardiac sodium channel splicing regulation of human heart failure
    Ge Gao
    Section of Cardiology, Department of Medicine, University of Illinois at Chicago and the Jesse Brown VA Medical Center, Chicago, IL 60612, USA
    Trends Cardiovasc Med 23:5-8. 2013
    ....
  27. pmc Dysfunctional resident lung mesenchymal stem cells contribute to pulmonary microvascular remodeling
    Kelsey Chow
    Department of Medicine, University of Colorado Denver, Aurora, Colorado, USA
    Pulm Circ 3:31-49. 2013
    ..These studies highlight an important role for microenviromental regulation of multipotent MSC function as well as their potential to contribute to tissue remodeling...
  28. pmc Immune cells control skin lymphatic electrolyte homeostasis and blood pressure
    Helge Wiig
    Department of Biomedicine, University of Bergen, Bergen, Norway
    J Clin Invest 123:2803-15. 2013
    ....
  29. pmc Unfolded protein response regulates cardiac sodium current in systolic human heart failure
    Ge Gao
    Lifespan Cardiovascular Research Center, The Warren Alpert School of Medicine, Brown University and Providence Veterans Administration Medical Center, Providence, RI
    Circ Arrhythm Electrophysiol 6:1018-24. 2013
    ..In this work, we tested whether truncated Na+ channels activate the unfolded protein response (UPR), contributing to SCN5A electric remodeling in HF...
  30. pmc Phosphofructokinase deficiency impairs ATP generation, autophagy, and redox balance in rheumatoid arthritis T cells
    Zhen Yang
    Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305
    J Exp Med 210:2119-34. 2013
    ....
  31. ncbi Immune mechanisms in medium and large-vessel vasculitis
    Cornelia M Weyand
    Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, CCSR Building Room 2225, Mail Code 5166, 269 Campus Drive West, Stanford, CA 94305 5166, USA
    Nat Rev Rheumatol 9:731-40. 2013
    ..Focusing on elements in the tissue context of GCA, instead of broadly suppressing host immunity, might enable a more tailored therapeutic approach that avoids unwanted adverse effects of aggressive immunosuppression...
  32. pmc T-cell aging in rheumatoid arthritis
    Cornelia M Weyand
    aDivision of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, California bDepartment of Medicine, Palo Alto Veteran Administration Healthcare System, Palo Alto, California, USA
    Curr Opin Rheumatol 26:93-100. 2014
    ..The process of immunosenescence is accelerated in rheumatoid arthritis (RA)...
  33. pmc Inflammation and mechanical stretch promote aortic stiffening in hypertension through activation of p38 mitogen-activated protein kinase
    Jing Wu
    From the Division of Clinical Pharmacology J W, S R T, A K, D W T, M A S, L X, M S M, W C, D G H, and Departments of Medicine and Pharmacology J W, D G H, Vanderbilt University, Nashville, TN and Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Egypt M A S
    Circ Res 114:616-25. 2014
    ..Hypertension is also associated with vascular inflammation and increased mechanical stretch. The interplay between inflammation, mechanical stretch, and aortic stiffening in hypertension remains undefined...
  34. pmc c-Src kinase inhibition reduces arrhythmia inducibility and connexin43 dysregulation after myocardial infarction
    Cody A Rutledge
    Department of Physiology, University of Illinois at Chicago, Chicago, Illinois Lifespan Cardiovascular Institute, The Warren Alpert School of Medicine of Brown University, and the Providence Veterans Administration Medical Center, Providence Rhode Island
    J Am Coll Cardiol 63:928-34. 2014
    ..The aim of this study was to evaluate the role of tyrosine kinase cellular-Src (c-Src) inhibition on connexin43 (Cx43) regulation in a mouse model of myocardial infarction (MI)...
  35. pmc Mechanisms shaping the naïve T cell repertoire in the elderly - thymic involution or peripheral homeostatic proliferation?
    Qian Qi
    Department of Medicine, Palo Alto Veterans Administration Health Care System, Palo Alto, CA 94304, United States Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, United States
    Exp Gerontol 54:71-4. 2014
    ..With increasing sequencing depth and the development of new statistical models, we are now in the position to test this model and to assess the impact of age on T cell diversity and clonality. ..
  36. pmc New diagnostic and therapeutic possibilities for diastolic heart failure
    Euy Myoung Jeong
    Assistant Professor of Medicine Research at The Cardiovascular Research Center CVRC at the Department of Medicine, Rhode Island Hospital and The Warren Alpert Medical School of Brown University
    R I Med J (2013) 97:35-7. 2014
    ..Here, we will review some promising new insights into the pathogenesis of diastolic dysfunction that may lead to new diagnostic and therapeutic tools...
  37. pmc Understanding immunosenescence to improve responses to vaccines
    Jorg J Goronzy
    The Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California, USA
    Nat Immunol 14:428-36. 2013
    ....
  38. ncbi Stress-dependent hypertension and the role of T lymphocytes
    Paul J Marvar
    Department of Psychiatry, Emory University School of Medicine, Atlanta, GA, USA
    Exp Physiol 97:1161-7. 2012
    ..This review discusses recent findings regarding the role of the central nervous system, T lymphocytes and the impact of cardiovascular risk factors, such as psychological stress, in hypertension...
  39. pmc Decline in miR-181a expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity
    Guangjin Li
    Department of Medicine, Stanford University School of Medicine, Stanford, California, USA
    Nat Med 18:1518-24. 2012
    ..DUSP6 is a potential intervention target for restoring T cell responses in the elderly, which may augment the effectiveness of vaccination...
  40. pmc Endoplasmic reticulum stress and hypertension - a new paradigm?
    Alyssa H Hasty
    Department of Molecular Physiology and Biophysics and Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 6602, USA
    J Clin Invest 122:3859-61. 2012
    ..This provides new insight into the molecular mechanisms that drive hypertension and suggests a potential target for future therapy...
  41. pmc Mitochondrial dysfunction causing cardiac sodium channel downregulation in cardiomyopathy
    Man Liu
    Section of Cardiology, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
    J Mol Cell Cardiol 54:25-34. 2013
    ..Reducing mitochondrial ROS by application of NAD(+), mitoTEMPO, PKC inhibitors, or PKA activators, restored I(Na). NAD(+) improved conduction velocity in human myopathic hearts...
  42. pmc Rapid and specific measurements of superoxide using fluorescence spectroscopy
    Rafal R Nazarewicz
    Vanderbilt University Medical Center, Nashville, TN 37212, USA
    J Biomol Screen 18:498-503. 2013
    ..We show that limitations of the HPLC-based analysis can be overcome by the optimized fluorescence spectroscopy...
  43. pmc Tetrahydrobiopterin improves diastolic dysfunction by reversing changes in myofilament properties
    Euy Myoung Jeong
    Department of Medicine, Section of Cardiology, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA
    J Mol Cell Cardiol 56:44-54. 2013
    ..These data provide evidence for modulation of cardiac relaxation by post-translational modification of myofilament proteins...
  44. pmc Role of the NADPH oxidases in the subfornical organ in angiotensin II-induced hypertension
    Heinrich E Lob
    Department of Biomedical Sciences, Cornell University, Ithaca, NY, USA
    Hypertension 61:382-7. 2013
    ....
  45. pmc The mosaic theory revisited: common molecular mechanisms coordinating diverse organ and cellular events in hypertension
    David G Harrison
    Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Am Soc Hypertens 7:68-74. 2013
    ..Thus, Page's Mosaic Theory formed a framework for future studies of molecular and cellular signals in the context of hypertension, and has greatly aided our understanding of this complex disease...
  46. pmc IL-7- and IL-15-mediated TCR sensitization enables T cell responses to self-antigens
    Pratima Deshpande
    Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
    J Immunol 190:1416-23. 2013
    ..We propose that HCs, possibly induced by lymphopenia, decrease the signaling threshold for TCR activation and are thereby partly responsible for autoimmunity in RA...
  47. pmc Nitric oxide reduces Cl⁻ absorption in the mouse cortical collecting duct through an ENaC-dependent mechanism
    Vladimir Pech
    Department of Medicine, Renal Division, Emory University School of Medicine, Atlanta, GA, USA
    Am J Physiol Renal Physiol 304:F1390-7. 2013
    ..We conclude that NO reduces Cl⁻ absorption in the CCD through a mechanism that is ENaC-dependent...
  48. pmc Mitochondria oxidative stress, connexin43 remodeling, and sudden arrhythmic death
    Ali A Sovari
    Section of Cardiology and Center for Cardiovascular Research, University of Illinois at Chicago, IL, USA
    Circ Arrhythm Electrophysiol 6:623-31. 2013
    ..Angiotensin-II activation increases reactive oxygen species (ROS) production, and ACE8/8 mice show increased cardiac ROS. We sought to determine the source of ROS and whether ROS played a role in the arrhythmogenesis...
  49. ncbi Targets of immune regeneration in rheumatoid arthritis
    Philipp J Hohensinner
    Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA
    Mayo Clin Proc 89:563-75. 2014
    ..With increasing knowledge of the molecular pathways that cause immunosenescence, therapeutic interventions can be designed to slow or halt the seemingly inevitable deterioration of protective immunity with aging...
  50. ncbi Essential role for the Menkes ATPase in activation of extracellular superoxide dismutase: implication for vascular oxidative stress
    Zhenyu Qin
    Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    FASEB J 20:334-6. 2006
    ..These studies provide a novel insight into vascular MNK as a critical modulator of "superoxide" stress, which may contribute to cardiovascular disease...
  51. ncbi Role of the multidrug resistance protein-1 in hypertension and vascular dysfunction caused by angiotensin II
    Julian D Widder
    Emory University, Division of Cardiology, Department of Medicine and the Atlanta Veterans Administration Hospital, Atlanta, GA 30322, USA
    Arterioscler Thromb Vasc Biol 27:762-8. 2007
    ..This can promotes thiol loss during states of increased glutathione oxidation. We investigated how MRP1 modulates blood pressure and vascular function during angiotensin II-induced hypertension...
  52. pmc Basic mechanisms of oxidative stress and reactive oxygen species in cardiovascular injury
    Christopher A Papaharalambus
    Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA 30322, USA
    Trends Cardiovasc Med 17:48-54. 2007
    ....
  53. pmc Measurement of reactive oxygen species in cardiovascular studies
    Sergey Dikalov
    Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA 30322, USA
    Hypertension 49:717-27. 2007
  54. ncbi Granulocyte colony-stimulating factor and granulocyte macrophage colony-stimulating factor exacerbate atherosclerosis in apolipoprotein E-deficient mice
    Amir Haghighat
    Cardiology Division, Emory University School of Medicine, 1639 Pierce Dr, Atlanta, GA 30322, USA
    Circulation 115:2049-54. 2007
    ..However, it is not known whether the short-term administration of G-CSF or GM-CSF exerts beneficial effects on atherosclerosis...
  55. pmc The role of the adventitia in vascular inflammation
    Kathryn Maiellaro
    Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology, GA, USA
    Cardiovasc Res 75:640-8. 2007
    ....
  56. ncbi NADPH oxidase inhibitors: new antihypertensive agents?
    Holly C Williams
    Division of Cardiology, Emory University, Atlanta, GA 30322, USA
    J Cardiovasc Pharmacol 50:9-16. 2007
    ..Targeting NADPH homologues may have a distinct advantage over current therapies because it would specifically prevent the pathophysiological formation of reactive oxygen species that contributes to hypertension...
  57. ncbi Endothelial NF-kappaB as a mediator of kidney damage: the missing link between systemic vascular and renal disease?
    Tomasz J Guzik
    Circ Res 101:227-9. 2007
  58. ncbi Regulation of tetrahydrobiopterin biosynthesis by shear stress
    Julian D Widder
    Division of Cardiology, Emory University, 101 Woodruff Circle, Atlanta, GA 30322, USA
    Circ Res 101:830-8. 2007
    ..These findings illustrate a new function of casein kinase 2 in the endothelium and provide insight into regulation of GTPCH-1 activity...
  59. ncbi In vivo imaging of hydrogen peroxide with chemiluminescent nanoparticles
    Dongwon Lee
    The Wallace H Coulter Department of Biomedical Engineering and Parker H Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, USA
    Nat Mater 6:765-9. 2007
    ..We anticipate numerous applications of peroxalate nanoparticles for in vivo imaging of hydrogen peroxide, given their high specificity and sensitivity and deep-tissue-imaging capability...
  60. ncbi Mitochondrial redox cycling of mitoquinone leads to superoxide production and cellular apoptosis
    Abdulrahman K Doughan
    Free Radical in Medicine CORE, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Antioxid Redox Signal 9:1825-36. 2007
    ..In light of these results, studies using mitoquinone as an antioxidant should be interpreted with caution...
  61. pmc Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction
    Tomasz J Guzik
    Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30033, USA
    J Exp Med 204:2449-60. 2007
    ..T cells might represent a novel therapeutic target for the treatment of high blood pressure...
  62. ncbi How does the chloride/proton antiporter ClC-3 control NADPH oxidase?
    BERNARD LASSEGUE
    Circ Res 101:648-50. 2007
  63. ncbi The role of osteopontin in recovery from hind limb ischemia
    Craig L Duvall
    Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, USA
    Arterioscler Thromb Vasc Biol 28:290-5. 2008
    ..In this study, we hypothesized that OPN plays a critical role in recovery from limb ischemia...
  64. ncbi Reactive oxygen species-selective regulation of aortic inflammatory gene expression in Type 2 diabetes
    Alejandra San Martin
    Division of Cardiology, Department of Medicine, Emory University, 1639 Pierce Dr, Atlanta, GA 30322, USA
    Am J Physiol Heart Circ Physiol 292:H2073-82. 2007
    ..The ability of Tempol to reverse ROS production as well as OPN and BMP-4, but not CTGF, induction suggests that DM-induced vascular inflammation involves both ROS-sensitive and -insensitive pathways...
  65. pmc Differential effects of AT1 receptor and Ca2+ channel blockade on atherosclerosis, inflammatory gene expression, and production of reactive oxygen species
    Derek E Doran
    Division of Cardiology, Department of Medicine, Emory University School of Medicine and the Atlanta VA Medical Center, Atlanta, GA, United States
    Atherosclerosis 195:39-47. 2007
    ..These data demonstrate that angiotensin II receptor blockade inhibits atherosclerosis by reducing vascular oxidative stress and inflammatory gene production independent of blood pressure reduction...
  66. ncbi Endothelial mechanotransduction, nitric oxide and vascular inflammation
    D G Harrison
    Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
    J Intern Med 259:351-63. 2006
    ..We will also review data that exercise training in vivo has a similar effect as laminar shear on endothelial function and discuss the clinical relevance of these basic findings...
  67. pmc Reactive oxygen species signaling in vascular smooth muscle cells
    Roza E Clempus
    Department of Medicine, Division of Cardiology, Emory University, 319 WMB, 1639 Pierce Dr Atlanta, GA 30322, USA
    Cardiovasc Res 71:216-25. 2006
    ..Therefore, it becomes critical to understand the different roles ROS play in the physiology and pathophysiology of VSMCs...
  68. ncbi Bone morphogenic protein-4 induces hypertension in mice: role of noggin, vascular NADPH oxidases, and impaired vasorelaxation
    Sumitra Miriyala
    Division of Cardiology, Emory University, Emory University, Atlanta, GA 30322, USA
    Circulation 113:2818-25. 2006
    ....
  69. ncbi Role of extracellular superoxide dismutase in hypertension
    Maria Carolina Gongora
    Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA
    Hypertension 48:473-81. 2006
    ..These compensatory mechanisms preserve large vessel function when ecSOD is absent in hypertension...
  70. ncbi Modulation of vascular smooth muscle signaling by reactive oxygen species
    Alicia N Lyle
    Department of Medicine, Division of Cardiology, Emory University, Atlanta, Georgia, USA
    Physiology (Bethesda) 21:269-80. 2006
    ..Identifying the precise intracellular targets of ROS enhances understanding of their role in cardiovascular physiology and pathophysiology...
  71. ncbi Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system
    Puja K Mehta
    Division of Cardiology, 319 WMB, Emory University, 1639 Pierce Drive, Atlanta, GA 30322, USA
    Am J Physiol Cell Physiol 292:C82-97. 2007
    ..This review focuses on the structure and function of AT(1) receptors and the major signaling mechanisms by which angiotensin influences cardiovascular physiology and pathology...
  72. pmc NADPH oxidases: new regulators of old functions
    Kathy K Griendling
    Antioxid Redox Signal 8:1443-5. 2006
  73. ncbi Mechanoregulation of monocyte chemoattractant protein-1 expression in rat vascular smooth muscle cells
    Thomas M Guest
    Division of Cardiology, Atlanta VAMC and Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Antioxid Redox Signal 8:1461-71. 2006
    ..These findings define a role for MAPK signal transduction in establishing a pro-inflammatory state in the arterial wall, and thus implicate a potential molecular link between arterial wall strain and atherosclerosis...
  74. pmc Nox4 is required for maintenance of the differentiated vascular smooth muscle cell phenotype
    Roza E Clempus
    Emory University, Division of Cardiology, 1639 Pierce Dr, Atlanta, GA 30322, USA
    Arterioscler Thromb Vasc Biol 27:42-8. 2007
    ..Reactive oxygen species (ROS) have been implicated in VSMC differentiation, but the responsible sources are unknown. In this study, we investigated the role of Nox1 and Nox4-derived ROS in this process...
  75. ncbi Impaired angiogenesis, early callus formation, and late stage remodeling in fracture healing of osteopontin-deficient mice
    Craig L Duvall
    Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA
    J Bone Miner Res 22:286-97. 2007
    ..Results showed that OPN plays an important role in regulation of angiogenesis, callus formation, and mechanical strength in early stages of healing and facilitates late stage bone remodeling and ECM organization...
  76. ncbi Mycophenolic acid is a new Nox2 inhibitor
    BERNARD LASSEGUE
    Hypertension 49:25-6. 2007
  77. ncbi Vitamin E reduces glomerulosclerosis, restores renal neuronal NOS, and suppresses oxidative stress in the 5/6 nephrectomized rat
    You Lin Tain
    Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida, USA
    Am J Physiol Renal Physiol 292:F1404-10. 2007
    ..An increased plasma asymmetric dimethylarginine occurred with 5/6 NX associated with decreased renal dimethylarginine dimethylaminohydrolase activity and increased type 1 protein arginine methyltransferase expression...
  78. pmc Production of extracellular superoxide by human lymphoblast cell lines: comparison of electron spin resonance techniques and cytochrome C reduction assay
    Sergey I Dikalov
    Free Radical in Medicine CORE, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA
    Biochem Pharmacol 73:972-80. 2007
    ..A highly sensitive in vitro measurement of O(2)(-) in human cell lines would allow investigators to study genotype/phenotype interactions in translational studies...
  79. ncbi Sad heart from no SOD
    Maria Carolina Gongora
    Hypertension 51:28-30. 2008
  80. ncbi Molecular mechanisms of angiotensin II-mediated mitochondrial dysfunction: linking mitochondrial oxidative damage and vascular endothelial dysfunction
    Abdulrahman K Doughan
    Division of Cardiology and Department of Medicine, Emory University School of Medicine, 1639 Pierce Dr, Atlanta, GA 30322, USA
    Circ Res 102:488-96. 2008
    ..Furthermore, mitochondrial dysfunction in response to Ang II modulates endothelial NO. and generation, which in turn has ramifications for development of endothelial dysfunction...
  81. pmc Induction of hypertension and peripheral inflammation by reduction of extracellular superoxide dismutase in the central nervous system
    Heinrich E Lob
    Division of Cardiology, Lowance Center of Human Immunology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
    Hypertension 55:277-83, 6p following 283. 2010
    ..These findings provide insight into how central signals produce vascular inflammation in response to hypertensive stimuli, such as angiotensin II...
  82. pmc Insufficient deactivation of the protein tyrosine kinase lck amplifies T-cell responsiveness in acute coronary syndrome
    Sergey Pryshchep
    Lowance Center for Human Immunology and Rheumatology, Emory University, Atlanta, GA, USA
    Circ Res 106:769-78. 2010
    ..The balance between protein phosphorylation and dephosphorylation defines the signal transduction threshold and determines appropriate T-cell responses...
  83. pmc Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction
    Meena S Madhur
    Division of Cardiology, Emory University, Atlanta, GA 30322, USA
    Hypertension 55:500-7. 2010
    ..We conclude that IL-17 is critical for the maintenance of angiotensin II-induced hypertension and vascular dysfunction and might be a therapeutic target for this widespread disease...
  84. pmc Uncoupled cardiac nitric oxide synthase mediates diastolic dysfunction
    GAD A SILBERMAN
    Department of Medicine Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA
    Circulation 121:519-28. 2010
    ..Similar events may occur in the heart that lead to uncoupled NOS and diastolic dysfunction...
  85. pmc Th17 and Th1 T-cell responses in giant cell arteritis
    Jiusheng Deng
    Division of Immunology and Rheumatology, Stanford University School of Medicine, 269 W Campus Dr, Stanford, CA 94305, USA
    Circulation 121:906-15. 2010
    ..The effects of glucocorticoids on the systemic and vascular components of GCA are not understood...
  86. pmc Role of the adaptive immune system in hypertension
    David G Harrison
    Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30345, USA
    Curr Opin Pharmacol 10:203-7. 2010
    ..Identification of these neoantigens and understanding how they form might prove useful in the prevention and treatment of this widespread and devastating disease...
  87. pmc Statins reduce endothelial cell apoptosis via inhibition of TRAIL expression on activated CD4 T cells in acute coronary syndrome
    Kayoko Sato
    Department of Cardiology, Tokyo Women s Medical University, 8 1 Kawada cho, Shinjyuku ku, Tokyo 162 8666, Japan
    Atherosclerosis 213:33-9. 2010
    ..We investigated whether statins can modulate cytotoxic functions of CD4 T cells in acute coronary syndrome (ACS)...
  88. pmc Therapeutic targeting of mitochondrial superoxide in hypertension
    Anna E Dikalova
    Division of Cardiology, Emory University School of Medicine, 1639 Pierce Dr, Atlanta, GA 30322, USA
    Circ Res 107:106-16. 2010
    ..It is possible that these agents are not adequately delivered to the subcellular sites of superoxide production...
  89. pmc Immune aging and rheumatoid arthritis
    Jorg J Goronzy
    Division of Immunology and Rheumatology, Department of Medicine, Stanford University, 269 West Campus Drive, Stanford, CA 94305 5166, USA
    Rheum Dis Clin North Am 36:297-310. 2010
    ....
  90. pmc Central and peripheral mechanisms of T-lymphocyte activation and vascular inflammation produced by angiotensin II-induced hypertension
    Paul J Marvar
    Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA
    Circ Res 107:263-70. 2010
    ..We have previously found that T lymphocytes are essential for development of angiotensin II-induced hypertension; however, the mechanisms responsible for T-cell activation in hypertension remain undefined...

Research Grants30

  1. CENTER FOR GASTROINTESTINAL BIOLOGY AND DISEASE
    Robert S Sandler; Fiscal Year: 2013
    ..Through all of its activities, the Center improves communication, promotes collaboration, develops careers and generally enriches the intellectual climate for digestive disease research. ..
  2. Pacific NorthWest Regional Center of Excellence (PNWRCE)
    Jay A Nelson; Fiscal Year: 2013
    ..pseudomallei host pathogen response during both the septicemic as well as the intracellular phases of the disease. ..