Publications
228 results found
Bhavsar PK, Brand NJ, Felkin LE, et al., 2010, Clenbuterol Induces Cardiac Myocyte Hypertrophy via Paracrine Signalling and Fibroblast-derived IGF-1, JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH, Vol: 3, Pages: 688-695, ISSN: 1937-5387
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- Citations: 13
Taegtmeyer AB, Breen JB, Smith J, et al., 2010, ATP-Binding Cassette Subfamily B Member 1 Polymorphisms Do Not Determine Cyclosporin Exposure, Acute Rejection or Nephrotoxicity After Heart Transplantation, TRANSPLANTATION, Vol: 89, Pages: 75-82, ISSN: 0041-1337
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- Citations: 12
Brand NJ, Lara-Pezzi E, Rosenthal N, et al., 2010, Analysis of Cardiac Myocyte Biology in Transgenic Mice: A Protocol for Preparation of Neonatal Mouse Cardiac Myocyte Cultures, MOUSE CELL CULTURE: METHODS AND PROTOCOLS, Vol: 633, Pages: 113-124, ISSN: 1064-3745
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- Citations: 16
Breckenridge RA, Zuberi Z, Gomes J, et al., 2009, Overexpression of the transcription factor Hand1 causes predisposition towards arrhythmia in mice, JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Vol: 47, Pages: 133-141, ISSN: 0022-2828
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- Citations: 22
Taegtmeyer AB, Breen JB, Rogers P, et al., 2009, Effect of Adenosine Monophosphate Deaminase-1 C34T Allele on the Requirement for Donor Inotropic Support and on the Incidence of Early Graft Dysfunction After Cardiac Transplantation, AMERICAN JOURNAL OF CARDIOLOGY, Vol: 103, Pages: 1457-1462, ISSN: 0002-9149
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- Citations: 7
Rider JE, Polster SP, Lee S, et al., 2009, Chronic treatment with clenbuterol modulates endothelial progenitor cells and circulating factors in a murine model of cardiomyopathy, Journal of Cardiovascular Translational Research, Vol: 2, Pages: 182-190, ISSN: 1937-5395
The purpose of this study was to determine the effects of chronic treatment with the beta 2 adrenergic receptor agonist clenbuterol on endothelial progenitor cells (EPC) in a well-characterized model of heart failure, the muscle LIM protein knockout (MLP−/−) mouse. MLP−/− mice were treated daily with clenbuterol (2 mg/kg) or saline subcutaneously for 6 weeks. Clenbuterol led to a 30% increase in CD31+ cells in the bone marrow of MLP−/− heart failure mice (p < 0.004). Clenbuterol did not improve ejection fraction. Clenbuterol treatment in MLP−/− mice was associated with significant changes in the following circulating factors: tissue inhibitor of metalloproteinase-type 1, leukemia inhibitory factor 1, C-reactive protein, apolipoprotein A1, fibroblast growth factor 2, serum glutamic oxaloacetic transaminase, macrophage-derived chemokine, and monocyte chemoattractant protein-3. Clenbuterol treatment in the MLP−/− model of heart failure did not rescue heart function, yet did increase CD31+ cells in the bone marrow. This is the first evidence that a beta 2 agonist increases EPC proliferation in the bone marrow in a preclinical model of heart failure.
Felkin LE, Lara-Pezzi E, George R, et al., 2009, Expression of Extracellular Matrix Genes During Myocardial Recovery From Heart Failure After Left Ventricular Assist Device Support, JOURNAL OF HEART AND LUNG TRANSPLANTATION, Vol: 28, Pages: 117-122, ISSN: 1053-2498
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- Citations: 44
Lara-Pezzi E, Terracciano CM, Soppa GK, et al., 2009, A gene expression profile of the myocardial response to clenbuterol, Journal of Cardiovascular Translational Research, Vol: 2, Pages: 191-197, ISSN: 1937-5395
Clenbuterol is currently being used as part of a clinical trial into a novel therapeutic approach for the treatment of end-stage heart failure. The purpose of this study was to determine the global pattern of myocardial gene expression in response to clenbuterol and to identify novel targets and pathways involved. Rats were treated with clenbuterol (n = 6) or saline (n = 6) for periods of 1, 3, 9, or 28 days. Rats treated for 28 days were also subject to continuous electrocardiogram analysis using implantable telemetry. RNA was extracted from rats at days 1 and 28 and used from microarray analysis, and further samples from rats at days 1, 3, 9, and 28 were used for analysis by real-time polymerase chain reaction. Clenbuterol treatment induced rapid development of cardiac hypertrophy with increased muscle mass at day 1 and elevated heart rate and QT interval throughout the 28-day period. Microarray analysis revealed a marked but largely transitory change in gene expression with 1,423 genes up-regulated and 964 genes down-regulated at day 1. Up-regulated genes revealed an unexpected association with angiogenesis and integrin-mediated cell adhesion and signaling. Moreover, direct treatment of endothelial cells cultured in vitro resulted in increased cell proliferation and tube formation. Our data show that clenbuterol treatment is associated with rapid cardiac hypertrophy and identify angiogenesis and integrin signaling as novel pathways of clenbuterol action. The data have implications both for our understanding of the physiologic hypertrophy induced by clenbuterol and for treatment of heart failure
Lara-Pezzi E, Felkin LE, Birks EJ, et al., 2008, Expression of Follistatin-Related Genes Is Altered in Heart Failure, ENDOCRINOLOGY, Vol: 149, Pages: 5822-5827, ISSN: 0013-7227
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- Citations: 66
Stagg MA, Carter E, Sohrabi N, et al., 2008, Cytoskeletal protein 4.1R affects repolarization and regulates calcium handling in the heart, CIRCULATION RESEARCH, Vol: 103, Pages: 855-U177, ISSN: 0009-7330
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- Citations: 41
Stagg MA, Carter E, Shorabi N, et al., 2008, Cytoskeletal protein 4.1R affects repolarization and regulates calcium handling in the heart, Circulation Research, Vol: 103, Pages: 855-863, ISSN: 0009-7330
Soppa GKR, Lee J, Stagg MA, et al., 2008, Role and possible mechanisms of clenbuterol in enhancing reverse remodelling during mechanical unloading in murine heart failure (vol 77, pg 695, 2008), CARDIOVASCULAR RESEARCH, Vol: 80, Pages: 159-159, ISSN: 0008-6363
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- Citations: 2
Fukushima S, Coppen SR, Lee J, et al., 2008, Choice of cell-delivery route for skeletal myoblast transplantation for treating post-infarction chronic heart failure in rat, PLOS One, Vol: 3, ISSN: 1932-6203
BackgroundIntramyocardial injection of skeletal myoblasts (SMB) has been shown to be a promising strategy for treating post-infarction chronic heart failure. However, insufficient therapeutic benefit and occurrence of ventricular arrhythmias are concerns. We hypothesised that the use of a retrograde intracoronary route for SMB-delivery might favourably alter the behaviour of the grafted SMB, consequently modulating the therapeutic effects and arrhythmogenicity.Methods and ResultsThree weeks after coronary artery ligation in female wild-type rats, 5×106 GFP-expressing SMB or PBS only (control) were injected via either the intramyocardial or retrograde intracoronary routes. Injection of SMB via either route similarly improved cardiac performance and physical activity, associated with reduced cardiomyocyte-hypertrophy and fibrosis. Grafted SMB via either route were only present in low numbers in the myocardium, analysed by real-time PCR for the Y-chromosome specific gene, Sry. Cardiomyogenic differentiation of grafted SMB was extremely rare. Continuous ECG monitoring by telemetry revealed that only intramyocardial injection of SMB produced spontaneous ventricular tachycardia up to 14 days, associated with local myocardial heterogeneity generated by clusters of injected SMB and accumulated inflammatory cells. A small number of ventricular premature contractions with latent ventricular tachycardia were detected in the late-phase of SMB injection regardless of the injection-route.ConclusionRetrograde intracoronary injection of SMB provided significant therapeutic benefits with attenuated early-phase arrhythmogenicity in treating ischaemic cardiomyopathy, indicating the promising utility of this route for SMB-delivery. Late-phase arrhythmogenicity remains a concern, regardless of the delivery route.
Birks EJ, Latif N, Enesa K, et al., 2008, Elevated p53 expression is associated with dysregulation of the ubiquitin-proteasome system in dilated cardiomyopathy, CARDIOVASCULAR RESEARCH, Vol: 79, Pages: 472-480, ISSN: 0008-6363
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- Citations: 92
Yamahara K, Fukushima S, Coppen SR, et al., 2008, Heterogeneic nature of adult cardiac side population cells, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 371, Pages: 615-620, ISSN: 0006-291X
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- Citations: 32
Soppa GKR, Barton PJR, Terracciano CMN, et al., 2008, Left ventricular assist device-induced molecular changes in the failing myocardium, CURRENT OPINION IN CARDIOLOGY, Vol: 23, Pages: 206-218, ISSN: 0268-4705
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- Citations: 29
Taegtmeyer AB, Rogers P, Breen JB, et al., 2008, The effects of pre- and post-transplant anemia on 1-year survival after cardiac transplantation, JOURNAL OF HEART AND LUNG TRANSPLANTATION, Vol: 27, Pages: 394-399, ISSN: 1053-2498
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- Citations: 16
Soppa GKR, Lee J, Stagg MA, et al., 2008, Role and possible mechanisms of clenbuterol in enhancing reverse remodelling during mechanical unloading in murine heart failure, Cardiovascular Research, Vol: 77, Pages: 695-706, ISSN: 1755-3245
AimsCombined left ventricular assist device (LVAD) and pharmacological therapy has been proposed to favour myocardial recovery in patients with end-stage heart failure (HF). Clenbuterol (Clen), a β2-adrenoceptor (β2-AR) agonist, has been used as a part of this strategy. In this study, we investigated the direct effects of clenbuterol on unloaded myocardium in HF.Methods and resultsLeft coronary artery ligation or sham operation was performed in male Lewis rats. After 4–6 weeks, heterotopic abdominal transplantation of the failing hearts into normal recipients was performed to induce LV unloading (UN). Recipient rats were treated with saline (Sal) or clenbuterol (2 mg/kg/day) via osmotic minipumps (HF + UN + Sal or HF + UN + Clen) for 7 days. Non-transplanted HF animals were treated with Sal (Sham + Sal, HF + Sal) or clenbuterol (HF + Clen). LV myocytes were isolated and studied using optical, fluorescence, and electrophysiological techniques. Clenbuterol treatment improved in vivo LV function measured with echocardiography (LVEF (%): HF 35.9 ± 2 [16], HF + Clen 52.1 ± 1.4 [16]; P < 0.001; mean ± SEM [n]). In combination with unloading, clenbuterol increased sarcomere shortening (amplitude (µm): HF + UN + Clen 0.1 ± 0.01 [50], HF + UN + Sal 0.07 ± 0.01 [38]; P < 0.001) by normalizing the depressed myofilament sensitivity to Ca2+ (slope of the linear relationship between Ca2+ transient and sarcomere shortening hysteresis loop during relaxation (μm/ratio unit): HF + UN + Clen 2.13 ± 0.2 [52], HF + UN + Sal 1.42 ± 0.13 [38]; P < 0.05).ConclusionClenbuterol treatment of failing rat hearts, alone or in combination with mechanical unloading, improves LV function at the whole-heart and cellular levels by affecting cell morphology, excitation–contraction coupling, and myofilament sensitivity to calcium. This study supports the use of this drug in the strategy to enhance recovery in HF pa
Lara-Pezzi E, Felkin LE, Birks E, et al., 2007, Myocardial follistatin gene expression is elevated in heart failure and decreases following recovery, Publisher: OXFORD UNIV PRESS, Pages: 787-787, ISSN: 0195-668X
Fukushima S, Varela-Carver A, Coppen SR, et al., 2007, Direct intramyocardial but not intracoronary injection of bone marrow cells induces ventricular arrhythmias in a rat chronic ischemic heart failure model, CIRCULATION, Vol: 115, Pages: 2254-2261, ISSN: 0009-7322
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- Citations: 152
Latif N, Yacoub MH, George R, et al., 2007, Changes in sarcomeric and non-sarcomeric cytoskeletal proteins and focal adhesion molecules during clinical myocardial recovery after left ventricular assist device support, JOURNAL OF HEART AND LUNG TRANSPLANTATION, Vol: 26, Pages: 230-235, ISSN: 1053-2498
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- Citations: 39
Hall JL, Birks EJ, Grindle S, et al., 2007, Molecular signature of recovery following combination left ventricular assist device (LVAD) support and pharmacologic therapy, EUROPEAN HEART JOURNAL, Vol: 28, Pages: 613-627, ISSN: 0195-668X
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- Citations: 79
Cullen ME, Barton PJR, 2007, Mapping transcriptional start sites and in silico DNA footprinting., Methods Mol Biol, Vol: 366, Pages: 203-216, ISSN: 1064-3745
Determination of a gene's transcriptional start site underlies the identification of the proximal promoter region and thus facilitates the subsequent analysis of components controlling its expression, namely, cis-acting regulatory elements and their cognate binding proteins. It also enables assembly of meaningful reporter constructs to examine promoter function in different cellular contexts. In this chapter, basic protocols for two experimental approaches to transcriptional start site determination are described: primer extension analysis and the ribonuclease protection assay. Consideration is also given to RNA sources, RNA purification, and primer design. The explosion in genomic DNA and mRNA sequence information derived from genomic sequencing projects, expressed sequence tags and microarrays, combined with in silico analysis, such as automated sequence annotation and gene identification algorithms, now provides an alternative source of detailed information on gene structure and expression. Two approaches to the in silico identification of transcription factor binding sites are described.
Felkin LE, Birks EJ, George R, et al., 2006, A quantitative gene expression profile of matrix metalloproteinases (MMPS) and their inhibitors (TIMPS) in the myocardium of patients with deteriorating heart failure requiring left ventricular assist device support, JOURNAL OF HEART AND LUNG TRANSPLANTATION, Vol: 25, Pages: 1413-1419, ISSN: 1053-2498
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- Citations: 52
Cullen ME, Yuen AHY, Felkin LE, et al., 2006, Myocardial expression of the arginine: Glycine amidinotransferase gene is elevated in heart failure and normalized after recovery - Potential implications for local creatine synthesis, CIRCULATION, Vol: 114, Pages: I16-I20, ISSN: 0009-7322
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- Citations: 81
Felkin LE, Birks EJ, Khaghani A, et al., 2006, Gene expression profile and regulation of MMPS and TIMPS in the myocardium of patients with deteriorating heart failure requiring LVAD support compared to stable end-stage heart failure, JOURNAL OF HEART AND LUNG TRANSPLANTATION, Vol: 25, Pages: S94-S95, ISSN: 1053-2498
Taegtmeyer AB, Barton PJR, Yacoub MH, 2006, Genetic association studies: personalized medicine in cardiac transplantation, NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE, Vol: 3, Pages: 58-59, ISSN: 1743-4297
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- Citations: 2
Raman M, Yacoub MH, Barton PJR, et al., 2006, Cloning of HCB1 & HCB2, two novel cardiac-enriched transcription factors, Annual Autumn Meeting of the British-Society-for-Cardiovascular-Research, Publisher: B M J PUBLISHING GROUP, ISSN: 1355-6037
Brand NJ, Barton PJR, Felkin LE, et al., 2006, Igf-1 transcription in cardiac myocytes and fibroblasts: Relevance to heart failure, Annual Autumn Meeting of the British-Society-for-Cardiovascular-Research, Publisher: B M J PUBLISHING GROUP, ISSN: 1355-6037
Felkin LE, Birks EJ, Soppa GK, et al., 2006, Matrix metalloproteinase (MMP) and tissue inhibitor of MMPs (TIMP) gene expression in myocardial recovery from heart failure, Annual Autumn Meeting of the British-Society-for-Cardiovascular-Research, Publisher: B M J PUBLISHING GROUP, ISSN: 1355-6037
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