G A Fitzgerald

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. pmc BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis
    R Daniel Rudic
    Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    PLoS Biol 2:e377. 2004
  2. doi request reprint Translational therapeutics at the platelet vascular interface. Summary
    Garret A Fitzgerald
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA
    Arterioscler Thromb Vasc Biol 28:s51-2. 2008
  3. ncbi request reprint Opinion: anticipating change in drug development: the emerging era of translational medicine and therapeutics
    Garret A Fitzgerald
    The Institute for Translational Medicine and Therapeutics, Room 805, Biomedical Research Building 2 3, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Nat Rev Drug Discov 4:815-8. 2005
  4. ncbi request reprint COX-2 inhibitors and the cardiovascular system
    G A Fitzgerald
    Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Clin Exp Rheumatol 19:S31-6. 2001
  5. ncbi request reprint Clinical pharmacology or translational medicine and therapeutics: reinvent or rebrand and expand?
    G A Fitzgerald
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Clin Pharmacol Ther 81:19-20. 2007
  6. ncbi request reprint Cardiovascular pharmacology of nonselective nonsteroidal anti-inflammatory drugs and coxibs: clinical considerations
    Garret A Fitzgerald
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Am J Cardiol 89:26D-32D. 2002
  7. ncbi request reprint COX-2 in play at the AHA and the FDA
    Garret A Fitzgerald
    Institute for Translational Medicine and Therapeutics, 153 Johnson Pavilion, School of Medicine, Hamilton Walk, University of Pennsylvania, PA 19104, USA
    Trends Pharmacol Sci 28:303-7. 2007
  8. ncbi request reprint COX-2 and beyond: Approaches to prostaglandin inhibition in human disease
    Garret A Fitzgerald
    Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Nat Rev Drug Discov 2:879-90. 2003
  9. ncbi request reprint Parsing an enigma: the pharmacodynamics of aspirin resistance
    Garret A Fitzgerald
    The Wellcome Trust Centre for Human Genetics, University of Oxford, OX3 7BN, Oxford, UK
    Lancet 361:542-4. 2003
  10. doi request reprint Translational therapeutics at the platelet vascular interface. Introduction
    Garret A Fitzgerald
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA
    Arterioscler Thromb Vasc Biol 28:s3-4. 2008

Research Grants

  1. Oxidative Modifications in Atherogenesis
    Garret FitzGerald; Fiscal Year: 2006
  2. Institutional Clinical and Translational Science Award
    Garret FitzGerald; Fiscal Year: 2007
  3. Institutional Clinical and Translational Science Award
    Garret FitzGerald; Fiscal Year: 2007
  4. Institutional Clinical and Translational Science Award
    Garret FitzGerald; Fiscal Year: 2007
  5. Lipids as Modulators of the Response to Vascular Injury
    Garret FitzGerald; Fiscal Year: 2007

Collaborators

Detail Information

Publications117 found, 100 shown here

  1. pmc BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis
    R Daniel Rudic
    Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    PLoS Biol 2:e377. 2004
    ..Furthermore, asynchronous dietary cues may modify glucose homeostasis via their interactions with peripheral molecular clocks...
  2. doi request reprint Translational therapeutics at the platelet vascular interface. Summary
    Garret A Fitzgerald
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA
    Arterioscler Thromb Vasc Biol 28:s51-2. 2008
  3. ncbi request reprint Opinion: anticipating change in drug development: the emerging era of translational medicine and therapeutics
    Garret A Fitzgerald
    The Institute for Translational Medicine and Therapeutics, Room 805, Biomedical Research Building 2 3, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Nat Rev Drug Discov 4:815-8. 2005
    ..The strategy of merger, pursued by many companies to compensate for the failure to develop new drugs, has, in most cases, compounded the problem, imposing geographic and cultural segregation on an already inefficient process...
  4. ncbi request reprint COX-2 inhibitors and the cardiovascular system
    G A Fitzgerald
    Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Clin Exp Rheumatol 19:S31-6. 2001
    ..However, evidence addressing directly this hypothesis is currently unavailable. On the other hand, coxib consumption alone does not currently warrant initiation of a cardioprotective regimen, such as low-dose aspirin...
  5. ncbi request reprint Clinical pharmacology or translational medicine and therapeutics: reinvent or rebrand and expand?
    G A Fitzgerald
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Clin Pharmacol Ther 81:19-20. 2007
  6. ncbi request reprint Cardiovascular pharmacology of nonselective nonsteroidal anti-inflammatory drugs and coxibs: clinical considerations
    Garret A Fitzgerald
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Am J Cardiol 89:26D-32D. 2002
    ....
  7. ncbi request reprint COX-2 in play at the AHA and the FDA
    Garret A Fitzgerald
    Institute for Translational Medicine and Therapeutics, 153 Johnson Pavilion, School of Medicine, Hamilton Walk, University of Pennsylvania, PA 19104, USA
    Trends Pharmacol Sci 28:303-7. 2007
    ..In this article, these actions of the AHA and the FDA are interpreted in the light of current knowledge, prompting the formulation of scientific questions that might be addressed...
  8. ncbi request reprint COX-2 and beyond: Approaches to prostaglandin inhibition in human disease
    Garret A Fitzgerald
    Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Nat Rev Drug Discov 2:879-90. 2003
  9. ncbi request reprint Parsing an enigma: the pharmacodynamics of aspirin resistance
    Garret A Fitzgerald
    The Wellcome Trust Centre for Human Genetics, University of Oxford, OX3 7BN, Oxford, UK
    Lancet 361:542-4. 2003
  10. doi request reprint Translational therapeutics at the platelet vascular interface. Introduction
    Garret A Fitzgerald
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA
    Arterioscler Thromb Vasc Biol 28:s3-4. 2008
  11. pmc Biosynthesis of 15-deoxy-delta12,14-PGJ2 and the ligation of PPARgamma
    L Chastine Bell-Parikh
    Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, 153 Johnson Pavilion, 3620 Hamilton Walk, Philadelphia, Pennsylvania 19104 6084, USA
    J Clin Invest 112:945-55. 2003
    ..15d-PGJ2 is not the endogenous mediator of PPARgamma-dependent adipocyte activation and is unaltered in clinical settings in which PPARgamma activation has been implicated...
  12. ncbi request reprint Regulation of cyclooxygenases by protein kinase C. Evidence against the importance of direct enzyme phosphorylation
    R Vezza
    Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 271:30028-33. 1996
    ..Despite regulated expression of COX-2 by PMA and the existence of consensus sequences for PKC phosphorylation, it appears that it is an unfavorable substrate for this enzyme...
  13. ncbi request reprint Cyclo-oxygenase products and atherothrombosis
    G A Fitzgerald
    Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia 19104, USA
    Ann Med 32:21-6. 2000
    ..By contrast, the effects of TP antagonists, aspirin, and even traditional NSAIDs on atherosclerotic plaque progression merit further evaluation in humans...
  14. ncbi request reprint Markers of platelet activation and oxidant stress in atherothrombotic disease
    G A Fitzgerald
    Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, USA
    Thromb Haemost 78:280-4. 1997
    ..Novel approaches to this problem promise the ability to study oxidative modification of proteins (46,66,67), lipids (57) and DNA (45,68) in clinical studies...
  15. ncbi request reprint Dietary factors in thrombosis and hemostasis: summary and conclusions
    G A Fitzgerald
    Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia 19104, USA
    Am J Clin Nutr 65:1699S-1701S. 1997
    ..Limited information is available as to health benefits of individual lipids, although drugs that lower cholesterol unequivocally reduce the incidence of cardiovascular death, even in patients with moderate hypercholesterolemia...
  16. ncbi request reprint Agonist-dependent phosphorylation of an epitope-tagged human prostacyclin receptor
    E M Smyth
    Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 271:33698-704. 1996
    ..These results indicate that the human prostacyclin receptor may be regulated by agonist-dependent phosphorylation. This appears to be mediated, in part, by activation of PKC but not by PKA...
  17. ncbi request reprint Lipid peroxidation and platelet activation in murine atherosclerosis
    T Cyrus
    Center for Experimental Therapeutics, Department of Pharmacology, University of Pennsylvania, Philadelphia, USA
    Circulation 104:1940-5. 2001
    ..Lipid peroxidation and platelet activation are thought to be important contributors to the pathogenesis of atherosclerosis. The relevance of their interaction in vivo, however, is unknown...
  18. ncbi request reprint Absence of 12/15-lipoxygenase expression decreases lipid peroxidation and atherogenesis in apolipoprotein e-deficient mice
    T Cyrus
    Center for Experimental Therapeutics, Department of Medicine, University of Pennsylvania, Philadelphia, USA
    Circulation 103:2277-82. 2001
    ....
  19. pmc Effect of regulated expression of human cyclooxygenase isoforms on eicosanoid and isoeicosanoid production in inflammation
    B F McAdam
    Center for Experimental Therapeutics, Department of Anesthesia, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Clin Invest 105:1473-82. 2000
    ....
  20. ncbi request reprint Local amplification of platelet function by 8-Epi prostaglandin F2alpha is not mediated by thromboxane receptor isoforms
    D Pratico
    Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 271:14916-24. 1996
    ..However, incidental activation of such a receptor by systemic concentrations of 8-epi PGF2alpha is unlikely to occur, even in syndromes of excessive free radical generation in vivo...
  21. ncbi request reprint Endogenous biosynthesis of thromboxane and prostacyclin in 2 distinct murine models of atherosclerosis
    D Pratico
    Center for Experimental Therapeutics, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104, USA
    Blood 96:3823-6. 2000
    ..Assessment of their generation in these models may afford the basis for future studies on the functional role of these eicosanoids in the evolution and progression of atherosclerosis. (Blood. 2000;96:3823-3826)..
  22. ncbi request reprint Effects of specific inhibition of cyclooxygenase-2 on sodium balance, hemodynamics, and vasoactive eicosanoids
    F Catella-Lawson
    University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania, USA
    J Pharmacol Exp Ther 289:735-41. 1999
    ..Our data suggest that acute sodium retention by nonsteroidal anti-inflammatory drugs in healthy elderly subjects is mediated by the inhibition of Cox-2, whereas depression of GFR is due to inhibition of Cox-1...
  23. ncbi request reprint Coxibs and cardiovascular disease
    Garret A Fitzgerald
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, USA
    N Engl J Med 351:1709-11. 2004
  24. ncbi request reprint Cyclooxygenase inhibitors and the antiplatelet effects of aspirin
    F Catella-Lawson
    EUPENN Group of Investigators, Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, Philadelphia 19104-6084, USA
    N Engl J Med 345:1809-17. 2001
    ..Treatment with ibuprofen in patients with increased cardiovascular risk may limit the cardioprotective effects of aspirin...
  25. pmc Acceleration of atherogenesis by COX-1-dependent prostanoid formation in low density lipoprotein receptor knockout mice
    D Pratico
    Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104 6160, USA
    Proc Natl Acad Sci U S A 98:3358-63. 2001
    ..Furthermore, evidence that COX-1-derived prostanoids contribute to atherogenesis suggests that controlled evaluation of the effects of nonsteroidal anti-inflammatory drugs and/or aspirin on plaque progression in humans is timely...
  26. ncbi request reprint Internalization and sequestration of the human prostacyclin receptor
    E M Smyth
    Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 275:32037-45. 2000
    ....
  27. ncbi request reprint Effects of vitamin E on lipid peroxidation in healthy persons
    E A Meagher
    Center for Experimental Therapeutics, 811 Biomedical Research Bldg II/III, University of Pennsylvania, 421 Curie Blvd, Philadelphia, PA 19104-6160, USA
    JAMA 285:1178-82. 2001
    ..Specific quantitative indices of oxidative stress in vivo should be considered as entry criteria and for dose selection in clinical trials of antioxidant drugs and vitamins in human disease...
  28. pmc Comparative impact on prostanoid biosynthesis of celecoxib and the novel nonsteroidal anti-inflammatory drug CG100649
    C Skarke
    Institute for Translational Medicine and Therapeutics ITMAT, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Clin Pharmacol Ther 91:986-93. 2012
    ..CG100649 and celecoxib are both relatively selective inhibitors of COX-2, but they differ in duration of action. Whether they have similar impact on cardiovascular events remains to be determined...
  29. ncbi request reprint Circulating autoantibodies to oxidized cardiolipin correlate with isoprostane F(2alpha)-VI levels and the extent of atherosclerosis in ApoE-deficient mice: modulation by vitamin E
    D Pratico
    The Center for Experimental Therapeutics, Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Blood 97:459-64. 2001
    ....
  30. ncbi request reprint Phosphorylation of the prostacyclin receptor during homologous desensitization. A critical role for protein kinase c
    E M Smyth
    Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 273:23258-66. 1998
    ..These results indicate that PKC-dependent phosphorylation is of critical importance to homologous regulation of hIP. Ser-328 is a primary site for PKC phosphorylation of hIP...
  31. ncbi request reprint Generation of 8-epiprostaglandin F2alpha by human monocytes. Discriminate production by reactive oxygen species and prostaglandin endoperoxide synthase-2
    D Pratico
    Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 271:8919-24. 1996
    ..8-Epi-PGF2alpha is a more abundant product of monocyte PG G/H S-2 than of platelet PG G/H S-1. Formation by inducible PG G/H S-2 must be considered as a source of this compound in vivo...
  32. ncbi request reprint COX-2-derived prostacyclin confers atheroprotection on female mice
    Karine M Egan
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, PA 19104, USA
    Science 306:1954-7. 2004
    ..This suggests that chronic treatment of patients with selective inhibitors of COX-2 could undermine protection from cardiovascular disease in premenopausal females...
  33. ncbi request reprint Reduction of isoprostanes and regression of advanced atherosclerosis by apolipoprotein E
    R K Tangirala
    Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 276:261-6. 2001
    ..In summary, these results demonstrate that liver-derived apoE directly induced regression of advanced atherosclerosis and has anti-oxidant properties in vivo that may contribute to its anti-atherogenic effects...
  34. doi request reprint Microsomal prostaglandin E synthase-1 inhibition in cardiovascular inflammatory disease
    M Wang
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA
    J Intern Med 263:500-5. 2008
    ..However, as the products of substrate rediversion vary according to cell type, these drugs may have contrasting impact amongst individuals at varied stages of disease evolution...
  35. ncbi request reprint Selective inhibitors of cyclooxygenase-2: a growing class of anti-inflammatory drugs
    I A Mardini
    Center for Experimental Therapeutics and Department of Anesthesia, University of Pennsylvania, Philadelphia, USA
    Mol Interv 1:30-8. 2001
    ....
  36. ncbi request reprint Oral glycoprotein IIb/IIIa antagonism in patients with coronary artery disease
    F Catella-Lawson
    EUPenn Group of Investigators at the Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Am J Cardiol 88:236-42. 2001
    ....
  37. ncbi request reprint Effect of the Pl(A2) alloantigen on the function of beta(3)-integrins in platelets
    J S Bennett
    Hematology Oncology Division, The Center for Experimental Therapeutics, and the General Clinical Research Center of the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Blood 97:3093-9. 2001
    ....
  38. ncbi request reprint Role of prostacyclin in the cardiovascular response to thromboxane A2
    Yan Cheng
    Center for Experimental Therapeutics, 153 Johnson Pavilion, 3620 Hamilton Walk, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
    Science 296:539-41. 2002
    ..This interplay may help explain the adverse cardiovascular effects associated with selective COX-2 inhibitors, which, unlike aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs), inhibit PGI2 but not TxA2...
  39. ncbi request reprint Prostaglandin F(2alpha) receptor-dependent regulation of prostaglandin transport
    R Vezza
    Center for Experimental Therapeutics, University of Pennsylvania, 153 Johnson Pavilion, 3600 Hamilton Walk, Philadelphia, PA 19104, USA
    Mol Pharmacol 59:1506-13. 2001
    ..This effect seems to be mediated via Galpha(s), independent of adenylate cyclase and cyclic AMP-dependent protein kinase activation...
  40. pmc Distinct roles of prostaglandin H synthases 1 and 2 in T-cell development
    B Rocca
    Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Clin Invest 103:1469-77. 1999
    ..COX-dependent PG generation may represent a mechanism of thymic stromal support for T-cell development...
  41. ncbi request reprint The isoprostanes in biology and medicine
    D Pratico
    The Center for Experimental Therapeutics, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104 6100, USA
    Trends Endocrinol Metab 12:243-7. 2001
    ..Finally, some F2-isoprostanes possess potent biological activities in vitro and in vivo, suggesting that they may also act as mediators of the cellular effects of oxidative stress...
  42. pmc Antimitogenic effects of HDL and APOE mediated by Cox-2-dependent IP activation
    Devashish Kothapalli
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104 6084, USA
    J Clin Invest 113:609-18. 2004
    ..Our results identify the Cox-2 gene as a target of APOE signaling, link HDL and APOE to IP action, and describe a potential new basis for the cardioprotective effect of HDL and APOE...
  43. ncbi request reprint Differential signaling by the thromboxane receptor isoforms via the novel GTP-binding protein, Gh
    R Vezza
    Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 274:12774-9. 1999
    ..Gh is expressed in platelets and vascular cells and may associate with both TP isoforms. However, stimulation of TP isoforms results in differential activation of downstream signaling pathways via this novel G protein...
  44. ncbi request reprint Regulation of CLOCK and MOP4 by nuclear hormone receptors in the vasculature: a humoral mechanism to reset a peripheral clock
    P McNamara
    Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cell 105:877-89. 2001
    ..We propose that circadian or periodic availability of nuclear hormones may play a critical role in resetting a peripheral vascular clock...
  45. ncbi request reprint Tetranor PGDM, an abundant urinary metabolite reflects biosynthesis of prostaglandin D2 in mice and humans
    Wen Liang Song
    Institute for Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 283:1179-88. 2008
    ..Niacin increased tetranor PGDM and 2,3-dinor-11beta-PGF(2alpha) in humans coincident with facial flushing. Tetranor PGDM is an abundant metabolite in urine that reflects modulated biosynthesis of PGD(2) in humans and mice...
  46. ncbi request reprint Central and peripheral clocks in cardiovascular and metabolic function
    Anne M Curtis
    The Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Ann Med 38:552-9. 2006
    ..The use of rodent models of disrupted clock function has begun to elucidate the role of the molecular clock in the pathophysiology of cardiovascular and metabolic disease...
  47. ncbi request reprint Marked interindividual variability in the response to selective inhibitors of cyclooxygenase-2
    Susanne Fries
    The Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6084, USA
    Gastroenterology 130:55-64. 2006
    ..We examined the variability in degree and selectivity of COX-2 inhibition in humans in response to celecoxib and rofecoxib...
  48. ncbi request reprint Peripheral circadian clocks in the vasculature
    Dermot F Reilly
    Institute for Translational Medicine and Therapeutics, 153 Johnson Pavilion, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Arterioscler Thromb Vasc Biol 27:1694-705. 2007
    ..This has raised the possibility that biological responses under the control of the molecular clock might interact with environmental cues to influence the phenotype of human cardiovascular disease...
  49. ncbi request reprint Functional characterization of the ocular prostaglandin f2alpha (PGF2alpha) receptor. Activation by the isoprostane, 12-iso-PGF2alpha
    P Kunapuli
    Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 272:27147-54. 1997
    ..Incidental receptor activation by isoprostanes may complement the actions of PGF2alpha in clinical syndromes where oxidant stress and augmented prostaglandin biosynthesis coincide...
  50. pmc The choreography of cyclooxygenases in the kidney
    G A Fitzgerald
    Center for Experimental Therapeutics, School of Medicine, 153 Johnson Pavillion, 3620 Hamilton Walk, University of Pennsylvania, Philadelphia, PA 19104 6084, USA
    J Clin Invest 110:33-4. 2002
  51. pmc Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities
    Tilo Grosser
    Institute for Translational Medicine and Therapeutics and Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Clin Invest 116:4-15. 2006
    ....
  52. doi request reprint Microsomal prostaglandin e2 synthase-1 modulates the response to vascular injury
    Miao Wang
    Institute for Translational Medicine and Therapeutics, Department of Pharmacology, University of Pennsylvania, Philadelphia, USA
    Circulation 123:631-9. 2011
    ..Indeed, deletion of mPGES-1 retards atherogenesis and angiotensin II-induced aortic aneurysm formation. The role of mPGES-1 in the response to vascular injury is unknown...
  53. pmc Prostaglandins and inflammation
    Emanuela Ricciotti
    Institute for Translational Medicine and Therapeutics, 153 Johnson Pavilion, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Arterioscler Thromb Vasc Biol 31:986-1000. 2011
    ..Prostaglandin biology has potential clinical relevance for atherosclerosis, the response to vascular injury and aortic aneurysm...
  54. ncbi request reprint Nonsteroidal anti-inflammatory drugs, coxibs, and cardio-renal physiology: a mechanism-based approach
    Garret A Fitzgerald
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Am J Cardiol 89:1D-2D. 2002
  55. ncbi request reprint COX-2-derived prostacyclin modulates vascular remodeling
    R Daniel Rudic
    The Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia 19104, USA
    Circ Res 96:1240-7. 2005
    ....
  56. pmc Cyclooxygenases, microsomal prostaglandin E synthase-1, and cardiovascular function
    Yan Cheng
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Clin Invest 116:1391-9. 2006
    ..These results suggest that inhibitors of mPGES-1 may retain their antiinflammatory efficacy by depressing PGE(2), while avoiding the adverse cardiovascular consequences associated with PGHS-2-mediated PGI(2) suppression...
  57. ncbi request reprint A prospective analysis of oxidative stress and liver transplantation
    Anne Burke
    Division of Gastroenterology, Departments of Medicine and Pharmacology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Transplantation 74:217-21. 2002
    ..Oxidative stress (OS) is a potential mechanism of injury in many deleterious complications of orthotopic liver transplantation (OLT). Therefore, we evaluated OS prospectively in a cohort of 50 adult patients before, during, and after OLT...
  58. doi request reprint Genetic components of the circadian clock regulate thrombogenesis in vivo
    Elizabeth J Westgate
    Institute for Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, Philadelphia, USA
    Circulation 117:2087-95. 2008
    ..Although genes relevant to hemostasis and vascular integrity undergo circadian oscillation, the role of the molecular clock in thrombotic events remains to be established...
  59. doi request reprint Perestroika in pharma: evolution or revolution in drug development?
    Garret A Fitzgerald
    University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    Mt Sinai J Med 77:327-32. 2010
    ..A failure to respond threatens the United States' lead in biomedical science and in the development and regulation of novel therapeutics...
  60. doi request reprint The role of clock genes in pharmacology
    Georgios K Paschos
    Department of Pharmacology, Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA
    Annu Rev Pharmacol Toxicol 50:187-214. 2010
    ..In this review, we provide evidence supporting the regulation of drug kinetics and dynamics by the circadian clock. We also use the examples of hypertension and cancer to show current achievements and challenges in chronopharmacology...
  61. pmc Deletion of microsomal prostaglandin E synthase-1 does not alter ozone-induced airway hyper-responsiveness
    Miao Wang
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Pharmacol Exp Ther 334:63-8. 2010
    ..Pharmacologically targeting mPGES-1 may not predispose patients at risk to airway dysfunction...
  62. pmc Circadian clocks and vascular function
    Georgios K Paschos
    Department of Pharmacology, 153 Johnson Pavilion, 3620 Hamilton Walk, Philadelphia, PA 19104 6084
    Circ Res 106:833-41. 2010
    ..In this review, we describe changes in vascular function that result from genetic disruption of discrete elements of the circadian clock...
  63. doi request reprint Emotion recollected in tranquility: lessons learned from the COX-2 saga
    Tilo Grosser
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6084, USA
    Annu Rev Med 61:17-33. 2010
    ..Lessons drawn from how this saga unfolded are relevant to how we approach drug surveillance and regulation, integrate diversifed forms of information and might pursue a more personalized approach to drug efficacy and risk...
  64. ncbi request reprint No evidence for lipid peroxidation in severe preeclampsia
    C L Regan
    Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia 19104-6160, USA
    Am J Obstet Gynecol 185:572-8. 2001
    ..CONCLUSIONS: These results call into question the importance of oxidative stress in the disease and the biochemical rationale for clinical trials of antioxidants to prevent and treat preeclampsia...
  65. pmc Network features of the mammalian circadian clock
    Julie E Baggs
    Department of Pharmacology and the Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    PLoS Biol 7:e52. 2009
    ..We propose that these network features act in concert as a genetic buffering system to maintain clock function in the face of genetic and environmental perturbation...
  66. pmc Deletion of microsomal prostaglandin E synthase-1 augments prostacyclin and retards atherogenesis
    Miao Wang
    Institute for Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, 3620 Hamilton Walk, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 103:14507-12. 2006
    ..Inhibitors of mPGES-1 may be less likely than those selective for cyclooxygenase 2 to result in cardiovascular complications because of a divergent impact on the biosynthesis of PGI(2)...
  67. doi request reprint Microsomal prostaglandin E synthase-1 deletion suppresses oxidative stress and angiotensin II-induced abdominal aortic aneurysm formation
    Miao Wang
    Institute for Translational Medicine and Therapeutics, 153 Johnson Pavilion, University of Pennsylvania, 3620 Hamilton Walk, Philadelphia, PA 19104, USA
    Circulation 117:1302-9. 2008
    ..Deletion of mPGES-1 modulates experimentally evoked pain and inflammation and retards atherogenesis. The role of mPGES-1 in abdominal aortic aneurysm is unknown...
  68. pmc Targeted deletions of cyclooxygenase-2 and atherogenesis in mice
    Yiqun Hui
    School of Medicine, Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 153 Johnson Pavilion, Philadelphia, PA 19104, USA
    Circulation 121:2654-60. 2010
    ..Floxed mice were used to parse distinct cellular contributions of COX-2 in macrophages and T cells (TCs) to atherogenesis...
  69. pmc Prostaglandin F2alpha elevates blood pressure and promotes atherosclerosis
    Ying Yu
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 106:7985-90. 2009
    ..Blockade of the FP offers an approach to the treatment of hypertension and its attendant systemic vascular disease...
  70. pmc Differential impact of prostaglandin H synthase 1 knockdown on platelets and parturition
    Ying Yu
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    J Clin Invest 115:986-95. 2005
    ..PGHS1(Neo/Neo) mice provide a model of low-dose aspirin therapy that elucidates how prevention or delay of preeclampsia might be achieved without compromising reproductive function...
  71. ncbi request reprint Prostaglandin E synthases in zebrafish
    Barbara Pini
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia 19104 6084, USA
    Arterioscler Thromb Vasc Biol 25:315-20. 2005
    ..Located downstream of the cyclooxygenases, PGESs catalyze PGE(2) formation, and deletion of microsomal (m)-PGES-1 abrogates inflammation. We sought to characterize the developmental expression of COX and PGES in zebrafish...
  72. ncbi request reprint COX-2-dependent cardiac failure in Gh/tTG transgenic mice
    Zhibing Zhang
    Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
    Circ Res 92:1153-61. 2003
    ..Gh/tTG activation regulates expression of COX-2 and its products may differentially modulate cardiomyocyte commitment to cell death or survival...
  73. ncbi request reprint Activation of nuclear receptors by prostaglandins
    Tomomi Ide
    Center for Experimental Therapeutics, School of Medicine, University of Pennsylvania, 153 Johnson Pavilion, 3620 Hamilton Walk, Philadelphia, PA 19104 6084, USA
    Thromb Res 110:311-5. 2003
    ..The application of quantitatively precise and sensitive physicochemical methodology will enhance experiments designed to address this hypothesis...
  74. doi request reprint Ablation of cyclooxygenase-2 in forebrain neurons is neuroprotective and dampens brain inflammation after status epilepticus
    G E Serrano
    Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Neurosci 31:14850-60. 2011
    ..These findings point to a profound role of seizure-induced neuronal COX-2 expression in neuropathologies that accompany epileptogenesis...
  75. doi request reprint The translational therapeutics of prostaglandin inhibition in atherothrombosis
    Y Yu
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104 6084, USA
    J Thromb Haemost 7:222-6. 2009
    ....
  76. ncbi request reprint Histone acetyltransferase-dependent chromatin remodeling and the vascular clock
    Anne M Curtis
    Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 279:7091-7. 2004
    ..Temporal coactivator recruitment and HAT-dependent chromatin remodeling on the promoter of clock controlled genes in the vasculature permits the mammalian clock to orchestrate circadian gene expression...
  77. pmc Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function
    Dairong Wang
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 106:7548-52. 2009
    ..Inhibition of COX-2 in cardiomyocytes may contribute to heart failure in patients receiving nonsteroidal anti-inflammatory drugs specific for inhibition of COX-2...
  78. ncbi request reprint Directed vascular expression of human cysteinyl leukotriene 2 receptor modulates endothelial permeability and systemic blood pressure
    Yiqun Hui
    Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, USA
    Circulation 110:3360-6. 2004
    ..However, the distinct contribution of CysLT2R to the vascular actions of CysLTs has not been addressed...
  79. pmc Cyclooxygenase-2-dependent prostacyclin formation and blood pressure homeostasis: targeted exchange of cyclooxygenase isoforms in mice
    Ying Yu
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 153 Johnson Pavilion, Philadelphia, PA 19104, USA
    Circ Res 106:337-45. 2010
    ..Both traditional nonsteroidal antiinflammatory drugs (NSAIDs) that inhibit COX-1 and COX-2 and NSAIDs designed to be selective for inhibition of COX-2 cause sodium retention and elevate blood pressure...
  80. ncbi request reprint Cyclooxygenases, thromboxane, and atherosclerosis: plaque destabilization by cyclooxygenase-2 inhibition combined with thromboxane receptor antagonism
    Karine M Egan
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA
    Circulation 111:334-42. 2005
    ..We addressed this issue and the role of TxA2 in the promotion and regression of diffuse, established atherosclerosis in Apobec-1/LDLR double KOs (DKOs)...
  81. pmc Circadian variation of blood pressure and the vascular response to asynchronous stress
    Anne M Curtis
    Institute for Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, 153 Johnson Pavilion, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 104:3450-5. 2007
    ..Furthermore, the clock may influence the time-dependent incidence of cardiovascular events by controlling the integration of selective asynchronous stress responses with an underlying circadian rhythm in cardiovascular function...
  82. pmc Pulmonary embolism in a woman taking oral contraceptives and valdecoxib
    Elizabeth J Westgate
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    PLoS Med 2:e197. 2005
  83. pmc Developmental expression of functional cyclooxygenases in zebrafish
    Tilo Grosser
    Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, 153 Johnson Pavilion, 3620 Hamilton Walk, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 99:8418-23. 2002
    ..Both zCOX isoforms are genetically and functionally homologous to their mammalian orthologs. The zebrafish affords a tractable model system for the study of COX biology and development...
  84. pmc Peripheral circadian clock rhythmicity is retained in the absence of adrenergic signaling
    Dermot F Reilly
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
    Arterioscler Thromb Vasc Biol 28:121-6. 2008
    ..Molecular clocks have been described in the heart and the vasculature; however it is largely unknown how the suprachiasmatic nucleus (SCN) entrains these peripheral oscillators...
  85. pmc Effect of assay specificity on the association of urine 11-dehydro thromboxane B2 determination with cardiovascular risk
    M T Olson
    Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, MD, USA
    J Thromb Haemost 10:2462-9. 2012
    ....
  86. ncbi request reprint Isoprostane activation of the nuclear hormone receptor PPAR
    Peter McNamara
    Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA
    Adv Exp Med Biol 507:351-5. 2002
  87. ncbi request reprint F2-isoprostanes as indices of lipid peroxidation in inflammatory diseases
    Domenico Pratico
    Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA
    Chem Phys Lipids 128:165-71. 2004
    ..Moreover, measurement of F2-isoprostanes might provide a sensitive biochemical basis of dose-selection in studies of natural and synthetic antioxidants...
  88. pmc Fibrinogen beta-chain tyrosine nitration is a prothrombotic risk factor
    Ioannis Parastatidis
    Stokes Research Institute and Departments of Pediatrics and Pharmacology, Children s Hospital of Philadelphia and The University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 283:33846-53. 2008
    ..The data provide a novel biochemical risk factor that could explain epidemiological associations of oxidative stress and inflammation with thrombotic complications...
  89. ncbi request reprint Noninvasive assessment of the role of cyclooxygenases in cardiovascular health: a detailed HPLC/MS/MS method
    Wen Liang Song
    Institute for Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Methods Enzymol 433:51-72. 2007
    ..Included are the addition of stable isotope-labeled internal standards, solid phase extraction, and quantitation by liquid chromatography/tandem mass spectrometry using selected reaction monitoring (SRM) techniques...
  90. ncbi request reprint Genetic model of selective COX2 inhibition reveals novel heterodimer signaling
    Ying Yu
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 421 Curie Boulevard, BRB II III, Philadelphia, Pennsylvania 19104, USA
    Nat Med 12:699-704. 2006
    ..The heterodimerization of PGHS1-PGHS2 may explain how the ductus arteriosus closes normally at birth in mice expressing PGHS2 Y385F, but not in PGHS2-null mice...
  91. ncbi request reprint Targeted cyclooxygenase gene (ptgs) exchange reveals discriminant isoform functionality
    Ying Yu
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 282:1498-506. 2007
    ..These mice will provide a valuable reagent with which to elucidate the distinct roles of the COX enzymes in mammalian biology...
  92. ncbi request reprint Cardiovascular hazard and non-steroidal anti-inflammatory drugs
    Dairong Wang
    Institute for Translational Medicine and Therapeutics and the Department of Pharmacology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania, USA
    Curr Opin Pharmacol 5:204-10. 2005
    ..Although there is no information from randomized placebo-controlled trials, traditional non-steroidal anti-inflammatory drugs, such as naproxen, dicofenac and ibuprofen, might differ in their effects of cardiovascular biology...
  93. ncbi request reprint Bioinformatic analysis of circadian gene oscillation in mouse aorta
    R Daniel Rudic
    The Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA
    Circulation 112:2716-24. 2005
    ..Here, we undertake studies to globally assess circadian gene expression in murine aorta...
  94. ncbi request reprint Neurofurans, novel indices of oxidant stress derived from docosahexaenoic acid
    Wen Liang Song
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Biol Chem 283:6-16. 2008
    ..Measurement of the nFs may ultimately prove useful in diagnosis, timing, and selection of dose in the treatment and chemoprevention of neurodegenerative disease...
  95. ncbi request reprint Oxidative stress and smoking-induced vascular injury
    Anne Burke
    Gastrointestinal Division and the Center for Experimental Therapeutics, Hospital of the University of Pennsylvania, Philadelphia, PA 19104 6084, USA
    Prog Cardiovasc Dis 46:79-90. 2003
    ..The emergence and application of rational quantitatively reliable indexes of oxidant stress in vivo is likely to elucidate the relative contribution of oxidant stress to smoking-induced vascular injury...
  96. doi request reprint The influence of pravastatin and atorvastatin on markers of oxidative stress in hypercholesterolemic humans
    Bonnie Ky
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6160, USA
    J Am Coll Cardiol 51:1653-62. 2008
    ..The aim of this study was to determine the effects of pravastatin and atorvastatin on markers of oxidative stress in plasma...
  97. pmc Prostanoids in health and disease
    Emer M Smyth
    Institute for Translational Medicine and Therapeutics, University of Pennsylvania, PA 19104, USA
    J Lipid Res 50:S423-8. 2009
    ..This review summarizes the current knowledge on prostanoid generation and the roles of individual mediators, their biosynthetic pathways, and their receptors in health and disease...
  98. ncbi request reprint Platelet-active drugs: the relationships among dose, effectiveness, and side effects: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
    Carlo Patrono
    University of Rome La Sapienza, Via di Grottarossa 1035, 00189 Rome, Italy
    Chest 126:234S-264S. 2004
    ....
  99. ncbi request reprint Oxidative stress and cardiovascular injury: Part II: animal and human studies
    Kathy K Griendling
    Division of Cardiology, Emory University, Atlanta, GA, USA
    Circulation 108:2034-40. 2003
  100. ncbi request reprint Parecoxib, valdecoxib, and cardiovascular risk
    Curt D Furberg
    Circulation 111:249. 2005
  101. ncbi request reprint Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison
    Christopher P Cannon
    Thrombolysis in Myocardial Infarction TIMI Study Group, Cardiovascular Division, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Lancet 368:1771-81. 2006
    ..The MEDAL programme was designed to provide a precise estimate of thrombotic cardiovascular events with the COX-2 selective inhibitor etoricoxib versus the traditional NSAID diclofenac...

Research Grants10

  1. Oxidative Modifications in Atherogenesis
    Garret FitzGerald; Fiscal Year: 2006
    ..abstract_text> ..
  2. Institutional Clinical and Translational Science Award
    Garret FitzGerald; Fiscal Year: 2007
    ..This will permit the development of interdisciplinary structures designed, to foster and facilitate research and education in this emerging discipline. ..
  3. Institutional Clinical and Translational Science Award
    Garret FitzGerald; Fiscal Year: 2007
    ..This will permit the development of interdisciplinary structures designed to. foster and facilitate research and education in this emerging discipline. ..
  4. Institutional Clinical and Translational Science Award
    Garret FitzGerald; Fiscal Year: 2007
    ..This will permit the development of interdisciplinary structures designed to. foster and facilitate research and education in this emerging discipline. ..
  5. Lipids as Modulators of the Response to Vascular Injury
    Garret FitzGerald; Fiscal Year: 2007
    ..This will permit a truly translational approach using hypothesis based and unbiased methodologies to investigating the role of bioactive lipids in the response to vascular injury. ..