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| G A FitzgeraldSummaryAffiliation: University of Pennsylvania Country: USA Publications
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Publications
BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasisR 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...
Translational therapeutics at the platelet vascular interface. SummaryGarret A Fitzgerald
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA
Arterioscler Thromb Vasc Biol 28:s51-2. 2008
Opinion: anticipating change in drug development: the emerging era of translational medicine and therapeuticsGarret 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...
COX-2 inhibitors and the cardiovascular systemG 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...
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
Cardiovascular pharmacology of nonselective nonsteroidal anti-inflammatory drugs and coxibs: clinical considerationsGarret A Fitzgerald
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Am J Cardiol 89:26D-32D. 2002....
COX-2 in play at the AHA and the FDAGarret 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...
COX-2 and beyond: Approaches to prostaglandin inhibition in human diseaseGarret A Fitzgerald
Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Nat Rev Drug Discov 2:879-90. 2003
Parsing an enigma: the pharmacodynamics of aspirin resistanceGarret A Fitzgerald
The Wellcome Trust Centre for Human Genetics, University of Oxford, OX3 7BN, Oxford, UK
Lancet 361:542-4. 2003
Translational therapeutics at the platelet vascular interface. IntroductionGarret A Fitzgerald
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA
Arterioscler Thromb Vasc Biol 28:s3-4. 2008
Biosynthesis of 15-deoxy-delta12,14-PGJ2 and the ligation of PPARgammaL 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...
Regulation of cyclooxygenases by protein kinase C. Evidence against the importance of direct enzyme phosphorylationR 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...
Cyclo-oxygenase products and atherothrombosisG 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...
Markers of platelet activation and oxidant stress in atherothrombotic diseaseG 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...
Dietary factors in thrombosis and hemostasis: summary and conclusionsG 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...
Agonist-dependent phosphorylation of an epitope-tagged human prostacyclin receptorE 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...
Lipid peroxidation and platelet activation in murine atherosclerosisT 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...
Absence of 12/15-lipoxygenase expression decreases lipid peroxidation and atherogenesis in apolipoprotein e-deficient miceT Cyrus
Center for Experimental Therapeutics, Department of Medicine, University of Pennsylvania, Philadelphia, USA
Circulation 103:2277-82. 2001....
Effect of regulated expression of human cyclooxygenase isoforms on eicosanoid and isoeicosanoid production in inflammationB F McAdam
Center for Experimental Therapeutics, Department of Anesthesia, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Clin Invest 105:1473-82. 2000....
Local amplification of platelet function by 8-Epi prostaglandin F2alpha is not mediated by thromboxane receptor isoformsD 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...
Endogenous biosynthesis of thromboxane and prostacyclin in 2 distinct murine models of atherosclerosisD 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)..
Effects of specific inhibition of cyclooxygenase-2 on sodium balance, hemodynamics, and vasoactive eicosanoidsF 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...
Coxibs and cardiovascular diseaseGarret A Fitzgerald
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, USA
N Engl J Med 351:1709-11. 2004
Cyclooxygenase inhibitors and the antiplatelet effects of aspirinF 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...
Acceleration of atherogenesis by COX-1-dependent prostanoid formation in low density lipoprotein receptor knockout miceD 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...
Internalization and sequestration of the human prostacyclin receptorE M Smyth
Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 275:32037-45. 2000....
Effects of vitamin E on lipid peroxidation in healthy personsE 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...
Comparative impact on prostanoid biosynthesis of celecoxib and the novel nonsteroidal anti-inflammatory drug CG100649C 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...
Circulating autoantibodies to oxidized cardiolipin correlate with isoprostane F(2alpha)-VI levels and the extent of atherosclerosis in ApoE-deficient mice: modulation by vitamin ED Pratico
The Center for Experimental Therapeutics, Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA
Blood 97:459-64. 2001....
Phosphorylation of the prostacyclin receptor during homologous desensitization. A critical role for protein kinase cE 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...
Generation of 8-epiprostaglandin F2alpha by human monocytes. Discriminate production by reactive oxygen species and prostaglandin endoperoxide synthase-2D 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...
COX-2-derived prostacyclin confers atheroprotection on female miceKarine 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...
Reduction of isoprostanes and regression of advanced atherosclerosis by apolipoprotein ER 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...
Microsomal prostaglandin E synthase-1 inhibition in cardiovascular inflammatory diseaseM 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...
Selective inhibitors of cyclooxygenase-2: a growing class of anti-inflammatory drugsI A Mardini
Center for Experimental Therapeutics and Department of Anesthesia, University of Pennsylvania, Philadelphia, USA
Mol Interv 1:30-8. 2001....
Oral glycoprotein IIb/IIIa antagonism in patients with coronary artery diseaseF 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....
Effect of the Pl(A2) alloantigen on the function of beta(3)-integrins in plateletsJ 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....
Role of prostacyclin in the cardiovascular response to thromboxane A2Yan 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...
Prostaglandin F(2alpha) receptor-dependent regulation of prostaglandin transportR 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...
Distinct roles of prostaglandin H synthases 1 and 2 in T-cell developmentB 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...
The isoprostanes in biology and medicineD 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...
Antimitogenic effects of HDL and APOE mediated by Cox-2-dependent IP activationDevashish 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...
Differential signaling by the thromboxane receptor isoforms via the novel GTP-binding protein, GhR 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...
Regulation of CLOCK and MOP4 by nuclear hormone receptors in the vasculature: a humoral mechanism to reset a peripheral clockP 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...
Tetranor PGDM, an abundant urinary metabolite reflects biosynthesis of prostaglandin D2 in mice and humansWen 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...
Central and peripheral clocks in cardiovascular and metabolic functionAnne 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...
Marked interindividual variability in the response to selective inhibitors of cyclooxygenase-2Susanne Fries
The Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6084, USA
Gastroenterology 130:55-64. 2006..These sources of variability might be exploited to identify patients uniquely susceptible to benefit or at developing risk of cardiovascular complications...
Peripheral circadian clocks in the vasculatureDermot 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...
Functional characterization of the ocular prostaglandin f2alpha (PGF2alpha) receptor. Activation by the isoprostane, 12-iso-PGF2alphaP 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...
The choreography of cyclooxygenases in the kidneyG 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
Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunitiesTilo 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....
Microsomal prostaglandin e2 synthase-1 modulates the response to vascular injuryMiao 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...
Prostaglandins and inflammationEmanuela 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...
Nonsteroidal anti-inflammatory drugs, coxibs, and cardio-renal physiology: a mechanism-based approachGarret A Fitzgerald
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Am J Cardiol 89:1D-2D. 2002
COX-2-derived prostacyclin modulates vascular remodelingR Daniel Rudic
The Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia 19104, USA
Circ Res 96:1240-7. 2005....
Cyclooxygenases, microsomal prostaglandin E synthase-1, and cardiovascular functionYan 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...
A prospective analysis of oxidative stress and liver transplantationAnne 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...
Genetic components of the circadian clock regulate thrombogenesis in vivoElizabeth 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...
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...
The role of clock genes in pharmacologyGeorgios 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...
Deletion of microsomal prostaglandin E synthase-1 does not alter ozone-induced airway hyper-responsivenessMiao 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...
Circadian clocks and vascular functionGeorgios 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...
Emotion recollected in tranquility: lessons learned from the COX-2 sagaTilo 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...
No evidence for lipid peroxidation in severe preeclampsiaC 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...
Network features of the mammalian circadian clockJulie 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...
Deletion of microsomal prostaglandin E synthase-1 augments prostacyclin and retards atherogenesisMiao 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)...
Microsomal prostaglandin E synthase-1 deletion suppresses oxidative stress and angiotensin II-induced abdominal aortic aneurysm formationMiao 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...
Targeted deletions of cyclooxygenase-2 and atherogenesis in miceYiqun 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...
Prostaglandin F2alpha elevates blood pressure and promotes atherosclerosisYing 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...
Differential impact of prostaglandin H synthase 1 knockdown on platelets and parturitionYing 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...
Prostaglandin E synthases in zebrafishBarbara 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...
COX-2-dependent cardiac failure in Gh/tTG transgenic miceZhibing 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...
Activation of nuclear receptors by prostaglandinsTomomi 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...
Ablation of cyclooxygenase-2 in forebrain neurons is neuroprotective and dampens brain inflammation after status epilepticusG 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...
The translational therapeutics of prostaglandin inhibition in atherothrombosisY Yu
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104 6084, USA
J Thromb Haemost 7:222-6. 2009....
Histone acetyltransferase-dependent chromatin remodeling and the vascular clockAnne 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...
Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and functionDairong 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...
Directed vascular expression of human cysteinyl leukotriene 2 receptor modulates endothelial permeability and systemic blood pressureYiqun 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...
Cyclooxygenase-2-dependent prostacyclin formation and blood pressure homeostasis: targeted exchange of cyclooxygenase isoforms in miceYing 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...
Cyclooxygenases, thromboxane, and atherosclerosis: plaque destabilization by cyclooxygenase-2 inhibition combined with thromboxane receptor antagonismKarine M Egan
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA
Circulation 111:334-42. 2005..TP ligands, including COX-1 (but not COX-2)-derived TxA2, promote initiation and early progression of atherogenesis in Apobec-1/LDLR DKOs but appear unimportant in the maintenance of established disease...
Circadian variation of blood pressure and the vascular response to asynchronous stressAnne 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...
Pulmonary embolism in a woman taking oral contraceptives and valdecoxibElizabeth J Westgate
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
PLoS Med 2:e197. 2005
Developmental expression of functional cyclooxygenases in zebrafishTilo 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...
Peripheral circadian clock rhythmicity is retained in the absence of adrenergic signalingDermot 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...
Effect of assay specificity on the association of urine 11-dehydro thromboxane B(2) determination with cardiovascular riskM T Olson
Departments of Pathology Medicine, The Johns Hopkins School of Medicine, Baltimore, MD Department of Medicine, University of Massachusetts Medical School, Worcester, MA Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, USA
J Thromb Haemost 10:2462-9. 2012..Conclusion: Quantification of urine 11-dehydro TXB(2) by monoclonal antibody-based ELISA was confounded by interference from 11-dehydro-2,3-dinor TXB(2) which reduced the accuracy and clinical utility of this second-generation assay...
Isoprostane activation of the nuclear hormone receptor PPARPeter McNamara
Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA
Adv Exp Med Biol 507:351-5. 2002
F2-isoprostanes as indices of lipid peroxidation in inflammatory diseasesDomenico 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...
Fibrinogen beta-chain tyrosine nitration is a prothrombotic risk factorIoannis 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...
Noninvasive assessment of the role of cyclooxygenases in cardiovascular health: a detailed HPLC/MS/MS methodWen 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...
Genetic model of selective COX2 inhibition reveals novel heterodimer signalingYing 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...
Targeted cyclooxygenase gene (ptgs) exchange reveals discriminant isoform functionalityYing 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...
Cardiovascular hazard and non-steroidal anti-inflammatory drugsDairong 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...
Bioinformatic analysis of circadian gene oscillation in mouse aortaR Daniel Rudic
The Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA
Circulation 112:2716-24. 2005....
Neurofurans, novel indices of oxidant stress derived from docosahexaenoic acidWen 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...
Oxidative stress and smoking-induced vascular injuryAnne 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...
The influence of pravastatin and atorvastatin on markers of oxidative stress in hypercholesterolemic humansBonnie 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...
Prostanoids in health and diseaseEmer 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...
Platelet-active drugs: the relationships among dose, effectiveness, and side effects: the Seventh ACCP Conference on Antithrombotic and Thrombolytic TherapyCarlo Patrono
University of Rome La Sapienza, Via di Grottarossa 1035, 00189 Rome, Italy
Chest 126:234S-264S. 2004....
Oxidative stress and cardiovascular injury: Part II: animal and human studiesKathy K Griendling
Division of Cardiology, Emory University, Atlanta, GA, USA
Circulation 108:2034-40. 2003
Parecoxib, valdecoxib, and cardiovascular riskCurt D Furberg
Circulation 111:249. 2005
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 comparisonChristopher 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 Grants
- Oxidative Modifications in AtherogenesisGarret FitzGerald; Fiscal Year: 2006..abstract_text> ..
- Institutional Clinical and Translational Science AwardGarret FitzGerald; Fiscal Year: 2007..This will permit the development of interdisciplinary structures designed, to foster and facilitate research and education in this emerging discipline. ..
- Institutional Clinical and Translational Science AwardGarret FitzGerald; Fiscal Year: 2007..This will permit the development of interdisciplinary structures designed to. foster and facilitate research and education in this emerging discipline. ..
- Institutional Clinical and Translational Science AwardGarret FitzGerald; Fiscal Year: 2007..This will permit the development of interdisciplinary structures designed to. foster and facilitate research and education in this emerging discipline. ..
- Lipids as Modulators of the Response to Vascular InjuryGarret 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. ..
