%0 Journal Article
%~ PubMed
%A Grieve, Stuart M
%A Lønborg, Jacob
%A Mazhar, Jawad
%A Tan, Timothy C
%A Ho, Edwin
%A Liu, Chia-Chi
%A Lay, William
%A Gill, Anthony J
%A Kuchel, Philip
%A Bhindi, Ravinay
%A Figtree, Gemma A
%T Cardiac magnetic resonance imaging of rapid VCAM-1 up-regulation in myocardial ischemia-reperfusion injury.
%B European Biophysics Journal
%D 2013
%C Germany
%I Springer
%V 42
%N 1
%P 61-70
%@ 1432-1017
%X 
%Z FOR Codes: 100402


%0 Journal Article
%~ PubMed
%A Kanagaratnam, Logan
%A Lee, Adam
%A Whalley, David
%A Figtree, Gemma A
%T Overcoming Artifacts and Fears: Electrophysiology Study and Radiofrequency Ablation in a Parkinsonian Patient with Supraventricular Tachycardia and a Brain Neurostimulator.
%B Pacing and Clinical Electrophysiology
%D 2013
%C United States
%I Wiley-Blackwell Publishing, Inc.
%V 36
%N 1
%P e1-e3
%@ 1540-8159
%X With the ageing of the population and expanding use of deep brain stimulation in the treatment of various neurological and neuropsychiatric conditions, there will be an increasing number of patients with these devices who present with cardiac conditions necessitating electrophysiology studies (EPS). However, neurostimulator devices have been shown to cause significant artifacts on electrocardiography recordings. We present the case of a 53-year-old Parkinsonian woman with a brain neurostimulator device who underwent a successful EPS with radiofrequency ablation. (PACE 2011;XX:1-3).
%Z FOR Codes: 110904


%0 Journal Article
%~ PubMed
%A Figtree, Gemma A
%A Rasmussen, Helge H
%A Liu, Chia-Chi
%T Oxidative regulation of the na+-k+ pump in cardiac physiology and pathology: clarifying the published evidence.
%B Circulation Research
%D 2013
%C United States
%I Lippincott Williams & Wilkins
%V 112
%N 1
%P e1
%@ 0009-7330
%X 
%Z FOR Codes: 30405


%0 Journal Article
%~ PubMed
%A Lay, W N
%A Rayner, B S
%A Sabaretnam, T
%A Figtree, G A
%A Jackson, C
%A Hunyor, S N
%A Bhindi, R
%T Activated protein C improves left ventricular remodelling after ischemia-reperfusion injury in rats.
%B International Journal of Cardiology
%D 2012
%C Ireland
%I Elsevier Ireland Ltd
%V 159
%N 3
%P 246-248
%@ 0167-5273
%X 
%Z FOR Codes: 110201


%0 Journal Article
%~ PubMed
%A Huang, Alex L
%A Mathur, Manu
%A Figtree, Gemma A
%T Cardiac magnetic resonance characterization of an iatrogenic left ventricular apical pseudo- aneurysm.
%B European Heart Journal Cardiovascular Imaging
%D 2012
%C United Kingdom
%I Oxford University Press
%V 13
%N 12
%P 1000
%@ 2047-2412
%X 
%Z FOR Codes: 1102


%0 Journal Article
%~ PubMed
%A Buchholz, Stefan
%A Shakil, Ayesha
%A Figtree, Gemma A
%A Hansen, Peter S
%A Bhindi, Ravinay
%T Diagnosis and management of patent foramen ovale.
%B Postgraduate Medical Journal
%D 2012
%C United Kingdom
%I BMJ Group
%V 88
%N 1038
%P 217-225
%@ 1469-0756
%X The foramen ovale is a slit-like anatomical structure located in the interatrial wall of the fetal heart that enables right-to-left shunting during fetal development. Although this hole generally closes completely shortly after birth due to shifting pressures in the atrial chambers, it remains open, or ''patent'', in about 25% of cases representing a potential substrate for right-to-left shunting during adult life. A patent foramen ovale (PFO) is usually haemodynamically insignificant, even when large, but is the most common cause of right-to-left shunt. Large-diameter PFOs may act as a pathway for passage of thrombus, air, fat, vegetation or vasoactive substances from the venous to the arterial circulation, potentially causing paradoxical emboli and stroke, inappropriate decompression sickness in divers, platypnoea-orthodeoxia syndrome and aural migraine. Over the past two decades, the association between PFO and the occurrence of migraine and cryptogenic stroke, particularly in younger adults, has been subject to considerable controversy and debate. Currently, semi-invasive contrast-transoesophageal echocardiography is accepted as the gold standard to detect right-to-left shunt across a PFO, but other imaging modalities utilising contrast such as second-harmonic transthoracic echocardiogram, transcranial Doppler sonography, CT and cardiac MRI have been shown to have similar sensitivity and specificity in detecting a PFO when compared with transoesophageal echocardiography. In this review the authors discuss embryological origins, diagnostic measures and evidence-based treatment options for the prevention of PFO-related paradoxical embolism, with emphasis on cryptogenic stroke and migraine.
%Z FOR Codes: 110201


%0 Journal Article
%~ PubMed
%A Kozor, Rebecca
%A Nelson, G C
%A Figtree, Gemma A
%T Extensive mid-wall myocardial oedema after aborted sudden death in hypertrophic cardiomyopathy.
%B International journal of cardiology
%D 2012
%C Ireland
%I Elsevier Ireland Ltd
%V 154
%N 1
%P e14-5
%@ 0167-5273
%X 
%Z FOR Codes: 1102


%0 Journal Article
%~ PubMed
%A Ward, Michael R
%A Figtree, Gemma A
%T Letter by Ward and Figtree article, "mechanisms of myocardial infarction in women without angiographically obstructive coronary artery disease".
%B Circulation
%D 2012
%C United States
%I Lippincott Williams & Wilkins
%V 126
%N 6
%P e82
%@ 0009-7322
%X 
%Z FOR Codes: 110201


%0 Journal Article
%~ PubMed
%A Yan, Warren
%A Ward, Michael R
%A Nelson, Gregory
%A Figtree, Gemma A
%A Bhindi, Ravinay
%T Overcoming limited depth penetration of optical coherence tomography with wire bias.
%B JACC: Cardiovascular Interventions
%D 2012
%C United States
%I Elsevier Inc.
%V 5
%N 1
%P e1-e2
%@ 1876-7605
%X 
%Z FOR Codes: 110201


%0 Journal Article
%~ PubMed
%A Figtree, Gemma A
%A Karimi Galougahi, Keyvan
%A Liu, Chia-Chi
%A Rasmussen, Helge H
%T Oxidative regulation of the Na(+)-K(+) pump in the cardiovascular system: Oxidative regulation of the cardiac Na(+)-K(+) pump.
%B Free Radical Biology & Medicine
%D 2012
%C United States
%I Elsevier Inc.
%V 53
%N 
%P 2263-2268
%@ 0891-5849
%X 
%Z FOR Codes: 30405


%0 Journal Article
%~ PubMed
%A Murphy, John Conleth
%A Kozor, Rebecca
%A Figtree, Gemma A
%A Ward, Michael R
%A Bhindi, Ravinay
%T Percutaneous coronary intervention via the radial artery: comparison of procedural success in emergency versus non-emergency cases.
%B Cardiovascular Revascularization Medicine
%D 2012
%C United States
%I Elsevier Inc.
%V 13
%N 5
%P 277-280
%@ 1878-0938
%X 
%Z FOR Codes: 1102


%0 Journal Article
%~ PubMed
%A Murphy, John C
%A Kozor, Rebecca A
%A Figtree, Gemma
%A Hansen, Peter S
%A Rasmussen, Helge H
%A Ward, Michael R
%A Nelson, Gregory I C
%A Bhindi, Ravinay
%T Procedural and in-patient outcomes in patients aged 80 years or older undergoing contemporary primary percutaneous coronary intervention.
%B EuroIntervention
%D 2012
%C France
%I Europa Edition
%V 8
%N 8
%P 912-919
%@ 1969-6213
%X 
%Z FOR Codes: 1102


%0 Journal Article
%~ PubMed
%A Rowell, Alexandra
%A Figtree, Melanie
%A Dimmick, Simon
%A Kotsiou, George
%A Grieve, Stuart M
%A Figtree, Gemma A
%T Recurrent right ventricular echinococcosis characterized by cardiac magnetic resonance.
%B International Journal of Cardiology
%D 2012
%C Ireland
%I Elsevier Ireland Ltd
%V 158
%N 2
%P 293-294
%@ 0167-5273
%X 
%Z FOR Codes: 1102


%0 Journal Article
%~ PubMed
%A Fong, Laura S
%A Mathur, Manu
%A Bhindi, Ravinay
%A Figtree, Gemma A
%T Right atrial Merkel cell tumour metastasis characterization using a multimodality approach.
%B European Heart Journal
%D 2012
%C United Kingdom
%I Oxford University Press
%V 33
%N 17
%P 2205
%@ 0195-668X
%X 
%Z FOR Codes: 110201


%0 Journal Article
%~ PubMed
%A Liu, Chia-Chi
%A Garcia, Alvaro
%A Mahmmoud, Yasser A
%A Hamilton, Elisha J
%A Galougahi, Keyvan Karimi
%A Fry, Natasha A S
%A Figtree, Gemma A
%A Cornelius, Flemming
%A Clarke, Ronald J
%A Rasmussen, Helge H
%T Susceptibility of β1 Na+-K+ pump subunit to glutathionylation and oxidative inhibition depends on conformational state of pump
%B The Journal of Biological Chemistry
%D 2012
%C United States
%I American Society for Biochemistry and Molecular Bi
%V 287
%N 15
%P 12353-12364
%@ 1083-351X
%X Glutathionylation of cysteine 46 of the ?1 subunit of the Na(+)-K(+) pump causes pump inhibition. However, the crystal structure, known in a state analogous to an E2·2K(+)·P(i) configuration, indicates that the side chain of cysteine 46 is exposed to the lipid bulk phase of the membrane and not expected to be accessible to the cytosolic glutathione. We have examined whether glutathionylation depends on the conformational changes in the Na(+)-K(+) pump cycle as described by the Albers-Post scheme. We measured ?1 subunit glutathionylation and function of Na(+)-K(+)-ATPase in membrane fragments and in ventricular myocytes. Signals for glutathionylation in Na(+)-K(+)-ATPase-enriched membrane fragments suspended in solutions that preferentially induce E1ATP and E1Na(3) conformations were much larger than signals in solutions that induce the E2 conformation. Ouabain further reduced glutathionylation in E2 and eliminated an increase seen with exposure to the oxidant peroxynitrite (ONOO(-)). Inhibition of Na(+)-K(+)-ATPase activity after exposure to ONOO(-) was greater when the enzyme had been in the E1Na(3) than the E2 conformation. We exposed myocytes to different extracellular K(+) concentrations to vary the membrane potential and hence voltage-dependent conformational poise. K(+) concentrations expected to shift the poise toward E2 species reduced glutathionylation, and ouabain eliminated a ONOO(-)-induced increase. Angiotensin II-induced NADPH oxidase-dependent Na(+)-K(+) pump inhibition was eliminated by conditions expected to shift the poise toward the E2 species. We conclude that susceptibility of the ?1 subunit to glutathionylation depends on the conformational poise of the Na(+)-K(+) pump.
%Z FOR Codes: 30402 60109 60110


%0 Journal Article
%~ PubMed
%A Figtree, Gemma A
%A Lønborg, Jacob
%A Grieve, Stuart M
%A Ward, Michael R
%A Bhindi, Ravinay
%T Cardiac magnetic resonance imaging for the interventional cardiologist.
%B JACC. Cardiovascular Interventions
%D 2011
%C United States
%I Elsevier Inc.
%V 4
%N 2
%P 137-148
%@ 1876-7605
%X Cardiac magnetic resonance imaging is a noninvasive technique for assessing heart structure and function without the need for ionizing radiation. Its ability to precisely outline regions of myocardial ischemia and infarction gives it an important role in guiding interventional cardiologists in revascularization. Its ability to characterize and precisely quantify abnormal regurgitant flow volumes or abnormal shunts also makes it a valuable tool for many noncoronary interventions. This review will discuss the evidence for cardiac magnetic resonance in guiding complex therapies in the catheter laboratory, as well as practical issues that need to be addressed to allow the application of this powerful tool to an increasing number of our patients.
%Z FOR Codes: 1102


%0 Journal Article
%~ PubMed
%A Hamilton, Elisha J
%A Figtree, Gemma A
%A Rasmussen, Helge H
%T Consideration of natriuretic peptide receptor C.
%B Circulation Research
%D 2011
%C United States
%I Lippincott Williams & Wilkins
%V 108
%N 4
%P e4; author reply e5
%@ 0009-7330
%X 
%Z FOR Codes: 60602 601


%0 Journal Article
%~ PubMed
%A Bibert, Stephanie
%A Liu, Chia-Chi
%A Figtree, Gemma A
%A Garcia, Alvaro
%A Hamilton, Elisha J
%A Marassi, Francesca M
%A Sweadner, Kathleen J
%A Cornelius, Flemming
%A Geering, Kaethi
%A Rasmussen, Helge H
%T FXYD proteins reverse inhibition of the Na-K pump mediated by glutathionylation of its {beta}1 subunit.
%B The Journal of biological chemistry
%D 2011
%C United States
%I American Society for Biochemistry and Molecular Bi
%V 286
%N 21
%P 18562-72
%@ 1083-351X
%X The seven members of the FXYD protein family associate with the Na(+)-K(+) pump and modulate its activity. We investigated whether conserved cysteines in FXYD proteins are susceptible to glutathionylation and whether such reactivity affects Na(+)-K(+) pump function in cardiac myocytes and Xenopus oocytes. Glutathionylation was detected by immunoblotting streptavidin precipitate from biotin-GSH loaded cells or by a GSH antibody. Incubation of myocytes with recombinant FXYD proteins resulted in competitive displacement of native FXYD1. Myocyte and Xenopus oocyte pump currents were measured with whole-cell and two-electrode voltage clamp techniques, respectively. Native FXYD1 in myocytes and FXYD1 expressed in oocytes were susceptible to glutathionylation. Mutagenesis identified the specific cysteine in the cytoplasmic terminal that was reactive. Its reactivity was dependent on flanking basic amino acids. We have reported that Na(+)-K(+) pump ??(1) subunit glutathionylation induced by oxidative signals causes pump inhibition in a previous study. In the present study, we found that ??(1) subunit glutathionylation and pump inhibition could be reversed by exposing myocytes to exogenous wild-type FXYD3. A cysteine-free FXYD3 derivative had no effect. Similar results were obtained with wild-type and mutant FXYD proteins expressed in oocytes. Glutathionylation of the ??(1) subunit was increased in myocardium from FXYD1(-/-) mice. In conclusion, there is a dependence of Na(+)-K(+) pump regulation on reactivity of two specifically identified cysteines on separate components of the multimeric Na(+)-K(+) pump complex. By facilitating deglutathionylation of the ??(1) subunit, FXYD proteins reverse oxidative inhibition of the Na(+)-K(+) pump and play a dynamic role in its regulation.
%Z FOR Codes: 60110 60602 60111


%0 Journal Article
%~ PubMed
%A Ho, Edwin
%A Bhindi, Ravinay
%A Ashley, Euan A
%A Figtree, Gemma A
%T Genetic analysis in cardiovascular disease: a clinical perspective.
%B Cardiology in Review
%D 2011
%C United States
%I Lippincott Williams & Wilkins
%V 19
%N 2
%P 81-89
%@ 1538-4683
%X Many forms of cardiovascular disease (CVD) demonstrate heritability and thus a genetic contribution is likely. This is most evident when considering the "simple" Mendelian traits such as hypertrophic cardiomyopathy. However, family history also influences our assessment of patients with complex traits such as coronary artery disease, hypertension, and common forms of hypercholesterolemia, as observed in clinical practice. Recent research has led to advances in our understanding of the genetic basis of both the simple and complex forms of CVD. This review presents the current state of knowledge regarding major gene disorders, as well as more common, complex forms of CVD such as coronary artery disease. It discusses the fundamental approaches being used to identify the genetic basis of the various disease states, as well as the practical implications of the discoveries to clinicians. It also focuses on our need to assess the extent by which genetic analysis can alter our calculation of an individual''s risk of disease, and our ability to successfully target treatment that will modify this process.
%Z FOR Codes: 110201


%0 Journal Article
%~ PubMed
%A Galougahi, Keyvan Karimi
%A Harden, Michael
%A Maher, Richard
%A Gill, Anthony
%A Bhindi, Ravinay
%A Grieve, Stuart M
%A Brady, Peter
%A Figtree, Gemma A
%T Incremental Diagnostic Value of Magnetic Resonance Imaging in the Characterization of a Cardiac Mass.
%B Journal of the American College of Cardiology
%D 2011
%C United States
%I Elsevier Inc.
%V 58
%N 10
%P e19
%@ 0735-1097
%X 
%Z FOR Codes: 304


%0 Journal Article
%~ PubMed
%A Bhindi, Ravinay
%A Grieve, Stuart
%A Figtree, Gemma A
%T Micromyocardial infarction in apical hypertrophic cardiomyopathy with obliterative coronary artery bridging.
%B International journal of cardiology
%D 2011
%C Ireland
%I Elsevier Ireland Ltd
%V 151
%N 1
%P e24-5
%@ 0167-5273
%X 
%Z FOR Codes: 110320 110201


%0 Journal Article
%~ PubMed
%A Yu, Chung-Yao
%A Grieve, Stuart M
%A Brazier, David
%A Bhindi, Ravinay
%A Figtree, Gemma A
%T Post-infarct ventricular thrombus: a critical diagnosis made by cardiac magnetic resonance imaging.
%B Heart, Lung & Circulation
%D 2011
%C Australia
%I Elsevier Australia
%V 20
%N 6
%P 372-373
%@ 1443-9506
%X 
%Z FOR Codes: 304


%0 Journal Article
%~ PubMed
%A Montfort, Jessica
%A Maher, Richard
%A Grieve, Stuart M
%A Figtree, Gemma A
%T Syringomyelia: A rare extracardiac contributor to syncope detected incidentally by CMR.
%B International journal of cardiology
%D 2011
%C Ireland
%I Elsevier Ireland Ltd
%V 150
%N 2
%P e62-4
%@ 0167-5273
%X We describe an extracardiac finding of syringomyelia in CMR study of a patient who was being investigated to exclude an infiltrative cause for presumptive cardiogenic syncope. Extension of a syrinx to involve the sympathetic structures in the intermediolateral column of the spinal cord can lead to well-recognised autonomic disturbances including Horner''s syndrome. Autonomic control of the heart has also been shown to be impaired in patients with syringomyelia. We investigated a 20 year old man presented with a history of recurrent syncope triggered by pain, micturition and defaecation. The cardiac MRI findings were normal, however close inspection of the scout images was suggestive of a lower thoracic spinal cord syrinx - a finding later confirmed by dedicated spinal MRI. Subsequent neurological investigations were essentially normal. We suggest that syringomyelia-induced disruption of sympathetic fibres in the thoracic spinal cord is a plausible, but rare mechanism of syncope.
%Z FOR Codes: 110201


%0 Journal Article
%~ PubMed
%A Yu, Chung-Yao
%A Brazier, David
%A Bhindi, Ravinay
%A Figtree, Gemma A
%A Ward, Michael R
%T Use of computer tomography coronary angiography in assessment of aorto-ostial coronary disease.
%B International journal of cardiology
%D 2011
%C Ireland
%I Elsevier Ireland Ltd
%V 147
%N 1
%P 153-4
%@ 0167-5273
%X 
%Z FOR Codes: 1103 1102


%0 Journal Article
%~ PubMed
%A White, Caroline N
%A Liu, Chia-Chi
%A Garcia, Alvaro
%A Hamilton, Elisha J
%A Chia, Karin K M
%A Figtree, Gemma A
%A Rasmussen, Helge H
%T Activation of cAMP-dependent signaling induces oxidative modification of the cardiac Na+-K+ pump and inhibits its activity.
%B The Journal of biological chemistry
%D 2010
%C United States
%I American Society for Biochemistry and Molecular Bi
%V 285
%N 18
%P 13712-20
%@ 1083-351X
%X Cellular signaling can inhibit the membrane Na(+)-K(+) pump via protein kinase C (PKC)-dependent activation of NADPH oxidase and a downstream oxidative modification, glutathionylation, of the beta(1) subunit of the pump alpha/beta heterodimer. It is firmly established that cAMP-dependent signaling also regulates the pump, and we have now examined the hypothesis that such regulation can be mediated by glutathionylation. Exposure of rabbit cardiac myocytes to the adenylyl cyclase activator forskolin increased the co-immunoprecipitation of NADPH oxidase subunits p47(phox) and p22(phox), required for its activation, and increased superoxide-sensitive fluorescence. Forskolin also increased glutathionylation of the Na(+)-K(+) pump beta(1) subunit and decreased its co-immunoprecipitation with the alpha(1) subunit, findings similar to those already established for PKC-dependent signaling. The decrease in co-immunoprecipitation indicates a decrease in the alpha(1)/beta(1) subunit interaction known to be critical for pump function. In agreement with this, forskolin decreased ouabain-sensitive electrogenic Na(+)-K(+) pump current (arising from the 3:2 Na(+):K(+) exchange ratio) of voltage-clamped, internally perfused myocytes. The decrease was abolished by the inclusion of superoxide dismutase, the inhibitory peptide for the epsilon-isoform of PKC or inhibitory peptide for NADPH oxidase in patch pipette solutions that perfuse the intracellular compartment. Pump inhibition was also abolished by inhibitors of protein kinase A and phospholipase C. We conclude that cAMP- and PKC-dependent inhibition of the cardiac Na(+)-K(+) pump occurs via a shared downstream oxidative signaling pathway involving NADPH oxidase activation and glutathionylation of the pump beta(1) subunit.
%Z FOR Codes: 110201 60111 60109


%0 Journal Article
%~ PubMed
%A Buchholz, Stefan
%A Ward, Michael R
%A Bhindi, Ravinay
%A Nelson, Gregory I C
%A Figtree, Gemma A
%A Grieve, Stuart M
%T Cardiac thrombi in stress (tako-tsubo) cardiomyopathy: more than an apical issue?
%B Mayo Clinic Proceedings
%D 2010
%C United States
%I Dowden Health Media, Inc
%V 85
%N 9
%P 863-864
%@ 1942-5546
%X 
%Z FOR Codes: 110201


%0 Journal Article
%~ PubMed
%A Robaei, Daniel
%A Grieve, Stuart M
%A Nelson, G C
%A Bhindi, Ravinay
%A Figtree, Gemma A
%T Cocaine-induced epicardial coronary artery thrombosis resulting in extensive myocardial injury assessed by cardiac magnetic resonance imaging.
%B European heart journal
%D 2010
%C United Kingdom, France
%I Oxford University Press
%V 31
%N 20
%P 2446
%@ 0195-668X
%X 
%Z FOR Codes: 110201


%0 Journal Article
%~ PubMed
%A Buchholz, Stefan
%A Grieve, Stuart M
%A Maher, Richard
%A Figtree, Gemma A
%T Cocaine-induced myocardial injury seen as multiple mid-wall foci of late enhancement by contrast-enhanced cardiac magnetic resonance imaging.
%B European heart journal
%D 2010
%C United Kingdom, France
%I Oxford University Press
%V 31
%N 11
%P 1422
%@ 0195-668X
%X 
%Z FOR Codes: 110201


%0 Journal Article
%~ PubMed
%A Lønborg, Jacob
%A Mathur, Manu
%A Grieve, Stuart M
%A Bhindi, Ravinay
%A Ward, Michael
%A Lowe, Harry
%A McCrohon, Jane
%A Figtree, Gemma A
%T Constrictive pericarditis diagnosed by cardiac magnetic resonance.
%B Journal of the American College of Cardiology
%D 2010
%C United States
%I Elsevier Inc.
%V 56
%N 20
%P e39
%@ 0735-1097
%X 
%Z FOR Codes: 110201


%0 Journal Article
%~ PubMed
%A Testa, L
%A Biondi Zoccai, G G L
%A Valgimigli, M
%A Latini, R A
%A Pizzocri, S
%A Lanotte, S
%A Laudisa, M L
%A Brambilla, N
%A Ward, M R
%A Figtree, G A
%A Bedogni, F
%A Bhindi, R
%T Current concepts on antiplatelet therapy: focus on the novel thienopyridine and non-thienopyridine agents.
%B Advances in Hematology
%D 2010
%C United States
%I Hindawi Publishing Corporation
%V 2010
%N 
%P 595934
%@ 1687-9112
%X Thienopyridines are a class of drug targeting the platelet adenosine diphosphate (ADP) 2 receptor. They significantly reduce platelet activity and are therefore clinically beneficial in settings where platelet activation is a key pathophysiological feature, particularly myocardial infarction. Ticlopidine, the first of the class introduced to clinical practice, was soon challenged and almost completely replaced by clopidogrel for its better tolerability. More recently, prasugrel and ticagrelor have been shown to provide a more powerful antiplatelet action compared to clopidogrel but at a cost of higher risk of bleeding complications. Cangrelor, a molecule very similar to ticagrelor, is currently being evaluated against clopidogrel. Considering the key balance of ischemic protection and bleeding risk, this paper discusses the background to the development of prasugrel, ticagrelor, and cangrelor and aims to characterise their risk-benefit profile and possible implementation in daily practice.
%Z FOR Codes: 1103


%0 Journal Article
%~ PubMed
%A Figtree, G A
%A Guzik, T
%A Robinson, B G
%A Channon, K M
%A Watkins, H
%T Functional estrogen receptor alpha promoter polymorphism is associated with improved endothelial-dependent vasolidation.
%B International journal of cardiology
%D 2010
%C Ireland
%I Elsevier Ireland
%V 143
%N 2
%P 207-8
%@ 0167-5273
%X Estrogen receptor alpha (ERalpha) mediates beneficial actions on endothelial nitric oxide synthase (eNOS) and cholesterol metabolism. Genetic variations in the promoter of the ERalpha may therefore influence vascular function. We have identified a single nucleotide polymorphism (T>C) in the transcriptional element "ERNE" upstream of ERalpha which abolished the negative effect of this element in luciferase reporter assays and was associated with reduction in LDL cholesterol in a small association study. We have now examined for the association of this putative functional polymorphism with endothelial function. Endothelial-dependent relaxation (EDR) was measured in organ bath preparations of human saphenous vein obtained from 101 individuals (81 males and 20 females) undergoing coronary artery bypass surgery. The presence of the variant C allele was associated with enhanced EDR independently of hypercholesterolaemia, smoking and diabetes, as well as sex (ANOVA for ACh induced relaxation: p=0.033). In males, the presence of the C allele was associated with a 225% augmentation of endothelial-dependent relaxation compared to wild-type (55.5+/-10%; n=3 vs. 24.7+/-1%; n=78; p<0.001). In summary, a polymorphism in the ERalpha negative transcriptional element which results in increased transcription in vitro is associated with substantial augmentation of endothelial-dependent vasorelaxation.
%Z FOR Codes: 110201


%0 Journal Article
%~ PubMed
%A Grieve, Stuart M
%A Bhindi, Ravinay
%A Seow, Jason
%A Doyle, Aoife
%A Turner, Anita J
%A Tomka, Janos
%A Lay, William
%A Gill, Anthony
%A Hunyor, Stephen N
%A Figtree, Gemma A
%T Microvascular obstruction by intracoronary delivery of mesenchymal stem cells and quantification of resulting myocardial infarction by cardiac magnetic resonance.
%B Circulation. Heart Failure
%D 2010
%C United States
%I Lippincott Williams & Wilkins
%V 3
%N 3
%P e5-6
%@ 1941-3297
%X 
%Z FOR Codes: 110201


%0 Journal Article
%~ PubMed
%A Rasmussen, Helge H
%A Hamilton, Elisha J
%A Liu, Chia-Chi
%A Figtree, Gemma A
%T Reversible oxidative modification: implications for cardiovascular physiology and pathophysiology.
%B Trends in Cardiovascular Medicine
%D 2010
%C United States
%I Elsevier Inc.
%V 20
%N 3
%P 85-90
%@ 1873-2615
%X Reminiscent of phosphorylation, cellular signaling can induce reversible forms of oxidative modification of proteins with an impact on their function. Redox signaling can be coupled to cell membrane receptors for hormones and be a physiologic means of regulating protein function, whereas pathologic increases in oxidative stress may induce disease processes. Here we review the role of reversible oxidative modification of proteins in the regulation of their function with particular emphasis on the cardiac Na(+)-K(+) pump. We describe how protein-kinase-dependent activation of redox signaling, mediated by angiotensin receptors and ?? adrenergic receptors, induces glutathionylation of an identified cysteine residue in the ??(1) subunit of the ??/?? pump heterodimer; and we discuss how this may link neurohormonal abnormalities, increased oxidative stress, and cardiac myocyte Na(+) dysregulation and heart failure with important implications for treatment.
%Z FOR Codes: 60602 60111 60110


%0 Journal Article
%~ PubMed
%A Figtree, Gemma
%A Thiruvallapan, Nala
%A Brereton, John
%A Whalley, David
%A Tofler, Geoffrey
%T The effect of elevated right atrial pressure due to pulmonary emboli on detection of patent foramen ovale and potential paradoxical embolus.
%B Journal of Cardiovascular Medicine
%D 2010
%C United States, Italy
%I Lippincott Williams & Wilkins
%V 11
%N 1
%P 61-63
%@ 1558-2035
%X 
%Z FOR Codes: 1102


%0 Journal Article
%~ PubMed
%A Bundgaard, Henning
%A Liu, Chia-Chi
%A Garcia, Alvaro
%A Hamilton, Elisha J
%A Huang, Yifei
%A Chia, Karin K M
%A Hunyor, Stephen N
%A Figtree, Gemma A
%A Rasmussen, Helge H
%T {beta}3 Adrenergic Stimulation of the Cardiac Na+-K+ Pump by Reversal of an Inhibitory Oxidative Modification.
%B Circulation
%D 2010
%C United States
%I Lippincott Williams & Wilkins
%V 122
%N 
%P 2699-708
%@ 0009-7322
%X inhibition of L-type Ca(2+) current contributes to negative inotropy of ??(3) adrenergic receptor (??(3) AR) activation, but effects on other determinants of excitation-contraction coupling are not known. Of these, the Na(+)-K(+) pump is of particular interest because of adverse effects attributed to high cardiac myocyte Na(+) levels and upregulation of the ??(3) AR in heart failure.
%Z FOR Codes: 60602 60110 60111


%0 Journal Article
%~ PubMed
%A White, Caroline N
%A Figtree, Gemma A
%A Liu, Chia-Chi
%A Garcia, Alvaro
%A Hamilton, Elisha J
%A Chia, Karin K M
%A Rasmussen, Helge H
%T Angiotensin II inhibits the Na+-K+ pump via PKC-dependent activation of NADPH oxidase.
%B American Journal of Physiology: Cell Physiology
%D 2009
%C United States
%I American Physiological Society
%V 296
%N 4
%P C693-C700
%@ 0363-6143
%X The sarcolemmal Na(+)-K(+) pump, pivotal in cardiac myocyte function, is inhibited by angiotensin II (ANG II). Since ANG II activates NADPH oxidase, we tested the hypothesis that NADPH oxidase mediates the pump inhibition. Exposure to 100 nmol/l ANG II increased superoxide-sensitive fluorescence of isolated rabbit ventricular myocytes. The increase was abolished by pegylated superoxide dismutase (SOD), by the NADPH oxidase inhibitor apocynin, and by myristolated inhibitory peptide to epsilon-protein kinase C (epsilonPKC), previously implicated in ANG II-induced Na(+)-K(+) pump inhibition. A role for epsilonPKC was also supported by an ANG II-induced increase in coimmunoprecipitation of epsilonPKC with the receptor for the activated kinase and with the cytosolic p47(phox) subunit of NADPH oxidase. ANG II decreased electrogenic Na(+)-K(+) pump current in voltage-clamped myocytes. The decrease was abolished by SOD, by the gp91ds inhibitory peptide that blocks assembly and activation of NADPH oxidase, and by epsilonPKC inhibitory peptide. Since colocalization should facilitate NADPH oxidase-dependent regulation of the Na(+)-K(+) pump, we examined whether there is physical association between the pump subunits and NADPH oxidase. The alpha(1)-subunit coimmunoprecipitated with caveolin 3 and with membrane-associated p22(phox) and cytosolic p47(phox) NADPH oxidase subunits at baseline. ANG II had no effect on alpha(1)/caveolin 3 or alpha(1)/p22(phox) interaction, but it increased alpha(1)/p47(phox) coimmunoprecipitation. We conclude that ANG II inhibits the Na(+)-K(+) pump via PKC-dependent NADPH oxidase activation.
%Z FOR Codes: 60109 60111 110201


%0 Journal Article
%~ PubMed
%A Figtree, Gemma A
%A Noonan, Jonathon E
%A Bhindi, Ravinay
%A Collins, Peter
%T Estrogen Receptor Polymorphisms: Significance to Human Physiology, Disease and Therapy.
%B Recent patents on DNA & gene sequences
%D 2009
%C Netherlands
%I Bentham Science Publishers Ltd
%V 0
%N 0
%P 0
%@ 1872-2156
%X Other than its well-recognized effects on reproductive physiology, estrogen has important actions in a wide variety of other body systems with important examples including bone, blood vessels and the heart. These effects are seen in both females and males. Investigators have hypothesized those genetic variants in the genes coding for estrogen signaling proteins may cause variable sensitivity to the hormone and influence an individual''s estrogen-sensitive phenotypes. The most obvious candidate genes are the estrogen receptors alpha and beta (ER and). However, the regulation of these genes is complex and not well understood. Furthermore, their coding exons, and regulatory sequences are dispersed across large segments of the genome. A number of common polymorphisms have been identified in both ER and ER, with variable degrees of evidence of their direct biological significance and their association with human disease. The identification of genetic variations associated with altered estrogen response is of potential public health importance. Insights may be gained into the pathogenesis of estrogen sensitive diseases such as osteoporosis, breast cancer and cardiovascular disease contributing to the development and application of newer therapies for these disorders. Furthermore, genetic variants that alter sensitivity to estrogen may affect both therapeutic and harmful responses to exogenous estrogen administered in the form of the oral contraceptive pill or hormone replacement therapy. This clinical significance has led to the publication of a number of patents which will be reviewed.
%Z FOR Codes: 110299


%0 Journal Article
%~ PubMed
%A Bhindi, Ravinay
%A Figtree, Gemma A
%T Percutaneous coronary intervention versus coronary-artery bypass grafting.
%B The New England journal of medicine
%D 2009
%C United States
%I Massachusetts Medical Society
%V 360
%N 25
%P 2672; author reply 2674-5
%@ 1533-4406
%X 
%Z FOR Codes: 110299


%0 Journal Article
%~ PubMed
%A Figtree, G A
%A Robinson, B G
%A Channon, K M
%A Watkins, H
%T Polymorphism upstream of estrogen receptor alpha reverses negative regulation of transcription.
%B International journal of cardiology
%D 2009
%C Ireland
%I Elsevier Ireland
%V 144
%N 1
%P 86-8
%@ 0167-5273
%X 
%Z FOR Codes: 110201


%0 Journal Article
%~ PubMed
%A Figtree, Gemma A
%A Liu, Chia-Chi
%A Bibert, Stephanie
%A Hamilton, Elisha J
%A Garcia, Alvaro
%A White, Caroline N
%A Chia, Karin K M
%A Cornelius, Flemming
%A Geering, Kaethi
%A Rasmussen, Helge H
%T Reversible Oxidative Modification. A Key Mechanism of Na+-K+ Pump Regulation.
%B Circulation research
%D 2009
%C United States
%I Lippincott Williams & Wilkins
%V 105
%N 0
%P 185-93
%@ 0009-7330
%X Angiotensin II (Ang II) inhibits the cardiac sarcolemmal Na(+)-K(+) pump via protein kinase (PK)C-dependent activation of NADPH oxidase. We examined whether this is mediated by oxidative modification of the pump subunits. We detected glutathionylation of beta(1), but not alpha(1), subunits in rabbit ventricular myocytes at baseline. beta(1) Subunit glutathionylation was increased by peroxynitrite (ONOO(-)), paraquat, or activation of NADPH oxidase by Ang II. Increased glutathionylation was associated with decreased alpha(1)/beta(1) subunit coimmunoprecipitation. Glutathionylation was reversed after addition of superoxide dismutase. Glutaredoxin 1, which catalyzes deglutathionylation, coimmunoprecipitated with beta(1) subunit and, when included in patch pipette solutions, abolished paraquat-induced inhibition of myocyte Na(+)-K(+) pump current (I(p)). Cysteine (Cys46) of the beta(1) subunit was the likely candidate for glutathionylation. We expressed Na(+)-K(+) pump alpha(1) subunits with wild-type or Cys46-mutated beta(1) subunits in Xenopus oocytes. ONOO(-) induced glutathionylation of beta(1) subunit and a decrease in Na(+)-K(+) pump turnover number. This was eliminated by mutation of Cys46. ONOO(-) also induced glutathionylation of the Na(+)-K(+) ATPase beta(1) subunit from pig kidney. This was associated with a approximately 2-fold decrease in the rate-limiting E(2)-->E(1) conformational change of the pump, as determined by RH421 fluorescence. We propose that kinase-dependent regulation of the Na(+)-K(+) pump occurs via glutathionylation of its beta(1) subunit at Cys46. These findings have implications for pathophysiological conditions characterized by neurohormonal dysregulation, myocardial oxidative stress and raised myocyte Na(+) levels.
%Z FOR Codes: 110201 60109 30406


%0 Journal Article
%~ PubMed
%A Rasmussen, Helge H
%A Figtree, Gemma A
%A Krum, Henry
%A Bundgaard, Henning
%T The use of beta3-adrenergic receptor agonists in the treatment of heart failure.
%B Current opinion in investigational drugs
%D 2009
%C United Kingdom
%I Current Drugs
%V 10
%N 9
%P 955-962
%@ 1472-4472
%X As the beta3-adrenergic receptor (beta3-AR) mediates a negative inotropic effect, upregulation of this receptor in patients with heart failure is considered to be harmful and associated with disease progression. The development of beta3-AR antagonists has therefore been proposed as a potential therapeutic option for heart failure. However, as increased intracellular myocyte Na+ levels represent a key adverse pathophysiological feature of heart failure, and the beta3-AR mediates the stimulation of the only export route for Na+ - the Na+-K+ pump - the upregulation of this receptor may also represent a useful compensatory mechanism. Data from animal studies and circumstantial observations from clinical trials suggest that beta3-AR activation is beneficial in severe heart failure, and that beta3-AR agonists are a promising therapeutic option for the treatment of this disease.
%Z FOR Codes: 1102


%0 Journal Article
%~ PubMed
%A Figtree, Gemma A
%A Grieve, Stuart M
%A Speller, Bridget
%A Geiger, Mary-Jane
%A Robinson, Bruce G
%A Channon, Keith M
%A Ragoussis, Jiannis
%A Collins, Peter
%A Watkins, Hugh
%T A commonly occurring polymorphism upstream of the estrogen receptor alpha alters transcription and is associated with increased HDL.
%B Atherosclerosis
%D 2008
%C Ireland
%I Elsevier Ireland Ltd
%V 199
%N 2
%P 354-61
%@ 0021-9150
%X Given the role of estrogen in the regulation of lipid metabolism, we screened for functional polymorphisms in the estrogen receptor alpha (ER*), and examined for their influence on serum cholesterol.
%Z FOR Codes: 110399 110299


%0 Journal Article
%~ PubMed
%A William, Maged
%A Hamilton, Elisha J
%A Garcia, Alvaro
%A Bundgaard, Henning
%A Chia, Karin Km
%A Figtree, Gemma A
%A Rasmussen, Helge H
%T Natriuretic peptides stimulate the cardiac sodium pump via NPR-C coupled NOS activation.
%B American journal of physiology. Cell physiology
%D 2008
%C United States
%I American Physiological Society
%V 294
%N 4
%P C1067-73
%@ 0363-6143
%X Natriuretic peptides (NPs) and their receptors (NPRs) are expressed in the heart, but their effects on myocyte function are poorly understood. Because NPRs are coupled to synthesis of cGMP, an activator of the sarcolemmal Na(+)-K(+) pump, we examined whether atrial natriuretic peptide (ANP) regulates the pump. We voltage clamped rabbit ventricular myocytes and identified electrogenic Na(+)-K(+) pump current (arising from the 3:2 Na(+):K(+) exchange and normalized for membrane capacitance) as the shift in membrane current induced by 100 micromol/l ouabain. Ten nanomoles per liter ANP stimulated the Na(+)-K(+) pump when the intracellular compartment was perfused with pipette solutions containing 10 mmol/l Na(+) but had no effect when the pump was at near maximal activation with 80 mmol/l Na(+) in the pipette solution. Stimulation was abolished by inhibition of cGMP-activated protein kinase with KT-5823, nitric oxide (NO)-activated guanylyl cyclase with 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ), or NO synthase with N(G)-nitro-L-arginine methyl ester (L-NAME). Since synthesis of cGMP by NPR-A and NPR-B is not NO dependent or ODQ sensitive, we exposed myocytes to AP-811, a highly selective ligand for the NPR-C "clearance" receptor. It abolished ANP-induced pump stimulation. Conversely, the selective NPR-C agonist ANP(4-23) reproduced stimulation. The stimulation was blocked by l-NAME. To examine NO production in response to ANP(4-23), we loaded myocytes with the NO-sensitive fluorescent dye diacetylated diaminofluorescein-2 and examined them by confocal microscopy. ANP(4-23) induced a significant increase in fluorescence, which was abolished by L-NAME. We conclude that NPs stimulate the Na(+)-K(+) pump via an NPR-C and NO-dependent pathway.
%Z FOR Codes: 111601


%0 Journal Article
%~ PubMed
%A Rasmussen, Helge H
%A Figtree, Gemma
%T "Don't flog the heart!" - development of specific drug therapies for heart failure.
%B Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine
%D 2007
%C Australia
%I Australasian Academy of Critical Care Medicine
%V 9
%N 4
%P 364-369
%@ 1441-2772
%X Understanding the cellular and molecular biology of heart failure is essential to developing targeted and effective treatment. Investigators are divided in their belief regarding the primary abnormality and whether it lies in dysregulation of neurohormonal signalling; nitric oxide synthesis and oxidative stress; cellular energy supply; or cellular ions. Our research demonstrates that these independently studied pathways are, in fact, closely interrelated. The Na+-K+ pump is critical in the determination of intracellular sodium levels, which are elevated in heart failure. Drug therapies have been developed targeting the neurohormonal abnormalities seen in the clinical syndrome of heart failure. We have examined the effect of many of these medications on the activity of the Na+-K+ pump and observed a perfect correlation between the ability of the treatment to stimulate the pump and its clinical outcome. This is illustrated by the stimulation of the pump by inhibition of the renin- angiotensin signalling pathway, and by aldosterone antagonists. We have also examined the role of reactive oxygen species as mediators of angiotensin and adrenergic regulation of the pump, demonstrating that intracellular pathways activated by Beta(1)/Beta(2)-adrenoceptors and the angiotensin II type 1 receptor converge, with both activating NAD(P)H oxidase and inhibiting the Na+-K+ pump via oxidative stress. In contrast, targeted stimulation of the Beta(3)-receptor resulted in nitric oxide-dependent pump stimulation in vitro, and improvements in left ventricular function in a large-animal heart failure model. Further characterisation of the intricate pathways involved in the hormonal regulation of the myocyte and its response to heart failure may aid in specific targeting of therapy.
%Z FOR Codes: 111601


%0 Journal Article
%~ PubMed
%A White, Caroline N
%A Hamilton, Elisha J
%A Garcia, Alvaro
%A Wang, Dennis
%A Chia, Karin Km
%A Figtree, Gemma A
%A Rasmussen, Helge H
%T Opposing effects of coupled and uncoupled NOS activity on the Na+-K+ pump in cardiac myocytes.
%B American journal of physiology. Cell physiology
%D 2007
%C United States
%I American Physiological Society
%V 294
%N 0
%P C572-8
%@ 0363-6143
%X Pharmacological delivery of nitric oxide (NO) stimulates the cardiac Na(+)-K(+) pump. However, effects of NO synthesized by NO synthase (NOS) often differ from the effects of NO delivered pharmacologically. In addition, NOS can become "uncoupled" and preferentially synthesize O(2)(.-), which often has opposing effects to NO. We tested the hypothesis that NOS-synthesized NO stimulates Na(+)-K(+) pump activity, and uncoupling of NOS inhibits it. To image NO, we loaded isolated rabbit cardiac myocytes with 4,5-diaminofluorescein-2 diacetate (DAF-2 DA) and measured fluorescence with confocal microscopy. L-arginine (L-arg; 500 micromol/l) increased DAF-2 DA fluorescence by 51% compared with control (n = 8; P < 0.05). We used the whole cell patch-clamp technique to measure electrogenic Na(+)-K(+) pump current (I(p)). Mean I(p) of 0.35 +/- 0.03 pA/pF (n = 44) was increased to 0.48 +/- 0.03 pA/pF (n = 7, P < 0.05) by 10 micromol/l L-Arg in pipette solutions. This increase was abolished by NOS inhibition with radicicol or by NO-activated guanylyl cyclase inhibition with 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one. We next examined the effect of uncoupling NOS using paraquat. Paraquat (1 mmol/l) induced a 51% increase in the fluorescence intensity of O(2)(.-)-sensitive dye dihydroethidium compared with control (n = 9; P < 0.05). To examine the functional effects of uncoupling, we measured I(p) with 100 micromol/l paraquat included in patch pipette solutions. This decreased I(p) to 0.28 +/- 0.03 pA/pF (n = 12; P < 0.001). The paraquat-induced pump inhibition was abolished by superoxide dismutase (in pipette solutions). We conclude that NOS-mediated NO synthesis stimulates the Na(+)-K(+) pump, whereas uncoupling of NOS causes O(2)(.-)-mediated pump inhibition.
%Z FOR Codes: