Publications
89 results found
Felkin LE, Dries DL, Birks EJ, et al., 2011, Changes in endoplasmic reticulum stress are associated with myocardial recovery using mechanical unloading and pharmacological therapy, Publisher: OXFORD UNIV PRESS, Pages: 1096-1097, ISSN: 0195-668X
Felkin LE, Narita T, Germack R, et al., 2011, Calcineurin splicing variant calcineurin Aβ1 improves cardiac function after myocardial infarction without inducing hypertrophy., Circulation, Vol: 123, Pages: 2838-2847
Calcineurin is a calcium-regulated phosphatase that plays a major role in cardiac hypertrophy. We previously described that alternative splicing of the calcineurin Aβ (CnAβ) gene generates the CnAβ1 isoform, with a unique C-terminal region that is different from the autoinhibitory domain present in all other CnA isoforms. In skeletal muscle, CnAβ1 is necessary for myoblast proliferation and stimulates regeneration, reducing fibrosis and accelerating the resolution of inflammation. Its role in the heart is currently unknown.
Felkin LE, Lara-Pezzi EA, Hall JL, et al., 2011, Reverse Remodelling and Recovery from Heart Failure Are Associated with Complex Patterns of Gene Expression, JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH, Vol: 4, Pages: 321-331, ISSN: 1937-5387
- Author Web Link
- Cite
- Citations: 24
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
- Author Web Link
- Cite
- Citations: 13
Balatonyi B, Racz B, Reglodi D, et al., 2010, Abstracts of the Sixth International Symposium on Myocardial Cytoprotection: From Basic Science to Clinical Perspectives : October 7 to 9, 2010, Pécs, Hungary, Experimental and clinical cardiology, Vol: 15, Pages: 41-56, ISSN: 1205-6626
<h4>PURPOSE:</h4> Pituitary adenylate cyclase activating polypeptide (PACAP) is a widely distributed endogenous neuropeptide, also occurring in the cardiovascular system. Among others, PACAP has been suggested as a cardioprotective factor. It has been shown that PACAP inhibits cardiac fibrosis and protects cardiomyocytes against oxidative stress and in vitro ischemia/reperfusion. The aim of the present study was to investigate whether PACAP is protective in doxorubicin-induced cell death of cardiomyocytes. <h4>METHODS:</h4> Primary culture of neonatal rat cardiomyocytes was prepared from ventricular slices of 2-4-day-old Wistar rats. Non-treated cells served as control (Group I). In Group II 1 μM of doxorubicin was added to the media while in Group III cells were treated with 1 μM of doxorubicin together with 20 nM PACAP1-38. In Group IV to antagonize the effect of PACAP1-38, 250 nM of the PACAP antagonist PACAP6-38 was added simultaneously with 1 μM doxorubicin. Cells were exposed to the mentioned concentration of chemicals for 24 h. Viability of cells were measured by MTT assay, the amount of apoptotic cells was assessed by flow cytometry following annexin V/propidium iodide double staining. The rate of apoptosis was further examined by measuring caspase-3 activity and phospho-Bad using flow cytometry. <h4>RESULTS:</h4> In doxorubicin-treated group (II) a lower number of living cells was observed with an increase of apoptotic cells while PACAP administration (Group III) led to a significant increase in the percentage of living cells and reproducible decrease in the rate of apoptosis. This beneficial effect of PACAP1-38 was diminished by PACAP6-38. Furthermore, doxorubicin increased the activation of pro-apoptotic caspase-3 and decreased the phosphorylation of Bad, while simultaneous PACAP treatment reduced the caspase-3 activation and increased the level of phospho-Bad. PACAP antagonist abolished the advantageous effect
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
- Author Web Link
- Cite
- Citations: 22
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
- Author Web Link
- Cite
- 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
- Author Web Link
- Cite
- Citations: 66
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
- Author Web Link
- Cite
- 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.
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
- Author Web Link
- Cite
- Citations: 32
Brand NJ, Raman M, Felkin LE, et al., 2008, Differential expression of the human cardiac troponin I gene by nuclear factor 1-A isoforms generated through alternative splicing, Annual Scientific Conference of the British-Cardiovascular-Society/British-Society-for-Cardiovascular-Research, Publisher: B M J PUBLISHING GROUP, Pages: A52-A52, ISSN: 1355-6037
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, Sarathchandra P, et al., 2008, Follistatin gene expression in heart failure and myocardial recovery following LVAD combination therapy, 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation, Publisher: ELSEVIER SCIENCE INC, Pages: S220-S220, ISSN: 1053-2498
Felkin LE, Lara-Pezzi E, George R, et al., 2008, Extracellular matrix gene expression during myocardial recovery from heart failure following LVAD combination therapy, 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation, Publisher: ELSEVIER SCIENCE INC, Pages: S219-S219, ISSN: 1053-2498
Lara-Pezzi E, Felkin LE, George R, et al., 2008, HAND1 gene expression is associated mitochondrial energy pathways and is altered during myocardial recovery from heart failure following LVAD combination therapy, 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation, Publisher: ELSEVIER SCIENCE INC, Pages: S220-S220, ISSN: 1053-2498
Suzuki K, Fukushima S, Varela-Carver A, et al., 2007, Response to letter regarding article, "Direct Intramyocardial but Not Intracoronary Injection of Bone Marrow Cells Induces Ventricular Arrhythmias in a Rat Chronic Ischemic Heart Failure Model", CIRCULATION, Vol: 116, Pages: E555-E555, ISSN: 0009-7322
- Author Web Link
- Cite
- Citations: 2
Barton PJ, Felkin LE, Lara-Pezzi E, et al., 2007, HAND1 gene expression is down regulated during myocardial recovery from heart failure and is associated with mitochondrial energy pathways, 80th Annual Scientific Session of the American-Heart-Association, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 732-732, ISSN: 0009-7322
- Author Web Link
- Cite
- Citations: 1
Lara-Pezzi E, Felkin LE, Sarathchandra P, et al., 2007, A potentially novel role of the follistatin-activin pathway in heart failure and myocardial recovery following LVAD combination therapy, 80th Annual Scientific Session of the American-Heart-Association, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 541-541, ISSN: 0009-7322
- Author Web Link
- Cite
- Citations: 1
Felkin LE, Lara-Pezzi E, George R, et al., 2007, Myocardial expression of extracellular matrix genes during LVAD combination therapy - Relevance to recovery, 80th Annual Scientific Session of the American-Heart-Association, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 732-733, ISSN: 0009-7322
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
Lara-Pezzi E, Felkin LE, Birks E, et al., 2007, Follistatin gene expression is elevated in heart failure and decreases following recovery, 19th World Congress of the International-Society-for-Heart-Research, Publisher: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, Pages: S147-S147, ISSN: 0022-2828
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
- Author Web Link
- Cite
- Citations: 152
Chester AH, Azam R, Felkin LE, et al., 2007, Correlation between vascular responsiveness and expression of novel transcripts of the ET<sub>A</sub>-receptor in human vascular tissue, VASCULAR PHARMACOLOGY, Vol: 46, Pages: 181-187, ISSN: 1537-1891
- Author Web Link
- Cite
- Citations: 2
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
- Author Web Link
- Cite
- Citations: 79
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
- Author Web Link
- Cite
- Citations: 52
Farkasfalvi K, Felkin L, Latif N, et al., 2006, The apelin receptor mRNA levels and myocardial recovery in end-stage heart failure patients treated with left ventricular assist devices (LVADs), 79th Annual Scientific Session of the American-Heart-Association, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 484-484, ISSN: 0009-7322
- Author Web Link
- Cite
- Citations: 1
Yamahara K, Fukushima S, Varela-Carver A, et al., 2006, High-mobility group box 1 protein (HMGB1) released by cell transplantation plays an important role in the therapeutic effects for treating chronic ischemic heart failure, 79th Annual Scientific Session of the American-Heart-Association, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 566-567, ISSN: 0009-7322
Fukushima S, Varela-Carver A, Coppen SR, et al., 2006, Regardless of cell-delivery route, skeletal myoblast transplantation into chronic heart failure induces transient therapeutic effects with persistent arrhythmogenesis, 79th Annual Scientific Session of the American-Heart-Association, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 415-415, ISSN: 0009-7322
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.