Genomes and Genes
- Spotlight on endothelial progenitor cell inhibitors: short reviewThomas Thum
Medizinische Klinik, Kardiologie, Julius Maximilians Universitat Wurzburg, Germany
Vasc Med 10:S59-64. 2005..Drug-induced mobilization and improvement of EPC function, as well as reduction of EPC inhibitors, is likely to enhance endothelial function and reduce atherosclerotic processes...
- Age-dependent impairment of endothelial progenitor cells is corrected by growth-hormone-mediated increase of insulin-like growth-factor-1Thomas Thum
Universitat Wurzburg, Medizinische Klinik I Kardiologie, Wurzburg, Germany
Circ Res 100:434-43. 2007..Growth hormone-mediated increase in IGF-1 reverses age-related EPC dysfunction and may be a novel therapeutic strategy against vascular disorders with impairment of EPC...
- Tissue-specific effects of the nuclear factor kappaB subunit p50 on myocardial ischemia-reperfusion injuryStefan Frantz
Medizinische Klinik und Poliklinik I, Herz Kreislaufzentrum, Universitat Wurzburg, Wurzburg, Germany
Am J Pathol 171:507-12. 2007..Bone marrow transplantation experiments indicate that impaired NF-kappaB activation in p50 KO leukocytes attenuates cardiac damage...
- Bone marrow molecular alterations after myocardial infarction: Impact on endothelial progenitor cellsThomas Thum
Medizinische Klinik I, Kardiologie, Universitatsklinikum Wurzburg, Julius Maximilians Universitat, Josef Schneider Str 2, 97080 Wurzburg, Germany
Cardiovasc Res 70:50-60. 2006..However, potential underlying mechanisms have not yet been investigated...
- Microarray-based gene expression profiling to elucidate cellular responses to nitric oxide--a review from an analytical and biomedical point of viewThomas Thum
Bayerische Julius Maximilians Universität, Universitatsklinikum, Medizinische Klinik und Poliklinik I, Kardiologie, Wurzburg, Germany
J Chromatogr B Analyt Technol Biomed Life Sci 851:3-11. 2007..We also point out the limitations of general microarray-based gene expression analyses and especially when investigating the effects of NO...
- MicroRNAs: novel regulators in cardiac development and diseaseThomas Thum
Medizinische Klinik und Poliklinik I, Universitatsklinikum, Julius Maximilians Universitat, Josef Schneider Street 2, D 97080 Wurzburg, Germany
Cardiovasc Res 79:562-70. 2008..Finally, we focus on the development and use of miRNA antagonists (antagomirs) to target miRNAs in vivo, which may translate into novel therapeutic strategies for heart disease in the future...
- Differential effects of organic nitrates on endothelial progenitor cells are determined by oxidative stressThomas Thum
Department of Cardiology, University of Wurzburg, University Hospital, Wurzburg, Germany
Arterioscler Thromb Vasc Biol 27:748-54. 2007..Endothelial nitric oxide synthase (eNOS)-derived NO regulates EPC mobilization and function. Organic nitrates release NO, and therefore may favorably affect EPC biology...
- Endothelial nitric oxide synthase uncoupling impairs endothelial progenitor cell mobilization and function in diabetesThomas Thum
Universitatsklinikum, Medizinische Klinik I, Universitat Wurzburg, Josef Schneider Strasse 2, 97080 Wurzburg, Germany
Diabetes 56:666-74. 2007..Subsequent reduction of EPC levels and impairment of EPC function likely contributes to the pathogenesis of vascular disease in diabetes...
- MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failureThomas Thum
University of Wurzburg, University Hospital, Department of Internal Medicine I, Cardiology, Wurzburg, Germany
Circulation 116:258-67. 2007..Here we provide evidence that cardiac microRNAs, recently discovered key regulators of gene expression, contribute to the transcriptional changes observed in heart failure...
- Growth hormone treatment improves markers of systemic nitric oxide bioavailability via insulin-like growth factor-IThomas Thum
Universitatsklinikum, Medizinische Klinik I Kardiologie, 97080 Wurzburg, Germany
J Clin Endocrinol Metab 92:4172-9. 2007..We investigated whether improved systemic NO bioavailability and increased levels of EPC after GH treatment are related and mediated by the IGF-I...
- The dying stem cell hypothesis: immune modulation as a novel mechanism for progenitor cell therapy in cardiac muscleThomas Thum
Department of Clinical Cardiology, National Heart and Lung Institute, Imperial College of Medicine, London, United Kingdom
J Am Coll Cardiol 46:1799-802. 2005..This leads to reduced scar formation, repressed myocardial apoptosis, and improved cardiac outcome...
- Suppression of endothelial progenitor cells in human coronary artery disease by the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginineThomas Thum
Bayerische Julius Maximilians Universität, Medizinische Klinik I, Wurzburg, Germany
J Am Coll Cardiol 46:1693-701. 2005..We tested the hypothesis that asymmetric dimethylarginine (ADMA) may be an endogenous inhibitor of endothelial progenitor cells (EPCs)...
- Improvement in left ventricular remodeling by the endothelial nitric oxide synthase enhancer AVE9488 after experimental myocardial infarctionDaniela Fraccarollo
Medizinische Klinik und Poliklinik I, Universitatsklinikum, Julius Maximilians Universitat Wurzburg, Wurzburg, Germany
Circulation 118:818-27. 2008..In this study, we investigated whether the transcription enhancer of endothelial NO synthase (eNOS) AVE9488 improves cardiac remodeling and heart failure after experimental myocardial infarction (MI)...
- LOX-1 receptor blockade abrogates oxLDL-induced oxidative DNA damage and prevents activation of the transcriptional repressor Oct-1 in human coronary arterial endotheliumThomas Thum
Medizinische Klinik I, Kardiologie, Julius Maximilians Universitat, Josef Schneider Strasse 2, 97080 Wurzburg, Germany
J Biol Chem 283:19456-64. 2008..Taken collectively, oxLDL induced oxidative DNA damage and activation of Oct-1 to result in metabolic dysfunction of coronary arterial endothelium...
- Endogenous nitric oxide synthesis inhibitor asymmetric dimethyl L-arginine accelerates endothelial cell senescenceFortunato Scalera
Institute of Clinical Pharmacology, University Hospital, Otto von Guericke University, Magdeburg, Germany
Arterioscler Thromb Vasc Biol 24:1816-22. 2004..Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS), and its accumulation has been associated with cardiovascular disease. We aimed to investigate the role of ADMA in endothelial cell senescence...
- Urinary asymmetric dimethylarginine (ADMA) is a predictor of mortality risk in patients with coronary artery diseaseChristian Wolf
Institut für Molekulare und Translationale Therapiestrategien IMTTS, Medizinische Hochschule, Hannover, Germany
Int J Cardiol 156:289-94. 2012..Unlike circulating ADMA, very little is known about urinary ADMA and DMA concentrations and a predictive value in CAD patients...
- The IGF-1 receptor as a therapeutic target to improve endothelial progenitor cell functionFelix Fleissner
Julius Maximilians Universitat, Medizinische Klinik I Kardiologie, Wurzburg, Germany
Mol Med 14:235-7. 2008
- Effects of physical exercise on myocardial telomere-regulating proteins, survival pathways, and apoptosisChristian Werner
Klinik fur Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitatsklinikum des Saarlandes, Homburg Saar, Germany
J Am Coll Cardiol 52:470-82. 2008..The purpose of this study was to study the underlying molecular mechanisms of the protective cardiac effects of physical exercise...
- Inhibition of proteasome-mediated glucocorticoid receptor degradation restores nitric oxide bioavailability in myocardial endothelial cells in vitroKinga G Blecharz
University of Wurzburg, Department of Anaesthesia and Critical Care, Wurzburg, 97080, Germany
Biol Cell 106:219-35. 2014..One of the numerous side effects of dexamethasone therapy is hypertension arising from reduced release of the endothelium-derived vasodilator nitric oxide (NO)...
- TWIST1 regulates the activity of ubiquitin proteasome system via the miR-199/214 cluster in human end-stage dilated cardiomyopathyAnna Baumgarten
Center for Cardiovascular Research, Charite Medical School, Berlin, Germany Applied Cachexia Research, Department of Cardiology, Charite Medical School, Berlin, Germany
Int J Cardiol 168:1447-52. 2013..This might be connected to the activity of the ubiquitin-proteasome-system (UPS), as miR-199a has been suggested to regulate the ubiquitin E2 ligases Ube2i and Ube2g1...
- Recent patents on cardiovascular stem cellsMarten Jakob
Universitatsklinik, Medizinische Klinik I, Kardiologie, Wurzburg, Germany
Recent Pat Cardiovasc Drug Discov 3:59-72. 2008..A systematic overview on the current patent situation about use of stem cells in cardiovascular medicine should facilitate future decision making in the development of novel therapeutic strategies in regenerative medicine...
- Prevention of liver cancer cachexia-induced cardiac wasting and heart failureJochen Springer
Applied Cachexia Research, Department of Cardiology, Charite Medical School, Campus Virchow Klinikum, Berlin, Germany
Eur Heart J 35:932-41. 2014..Herein, we evaluate the effects of drugs commonly used to treat HF (bisoprolol, imidapril, spironolactone) on development of cardiac wasting, HF, and death in the rat hepatoma CC model (AH-130)...
- Role of miR-21 in the pathogenesis of atrial fibrosisOliver Adam
Klinik fur Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitatsklinikum des Saarlandes, Homburg Saar, Germany
Basic Res Cardiol 107:278. 2012..Activation of Rac1 by angiotensin II leads to a CTGF- and lysyl oxidase-mediated increase of miR-21 expression contributing to structural remodelling of the atrial myocardium...
- No effects of human ghrelin on cardiac function despite profound effects on body composition in a rat model of heart failureYoshihiro J Akashi
Division of Applied Cachexia Research, Department of Cardiology, Charite Medical School, Berlin, Germany
Int J Cardiol 137:267-75. 2009..Ghrelin, was observed to have treatment-potential for severe chronic heart failure (CHF) and cardiac cachexia based on anti-cachectic and cardio-protective effects...
- Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic ApproachesJulia Beermann
Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany and National Heart and Lung Institute, Imperial College London, London, United Kingdom
Physiol Rev 96:1297-325. 2016..We specifically focus on non-coding RNAs as potential therapeutic targets and diagnostic biomarkers. ..
- Bioinformatics of cardiovascular miRNA biologyMeik Kunz
Functional Genomics and Systems Biology Group, Department of Bioinformatics, Biocenter, Wurzburg, Germany Institute for Molecular and Translational Therapeutic Strategies IMTTS, Hannover Medical School, Hannover, Germany
J Mol Cell Cardiol 89:3-10. 2015..In addition, we discuss drawbacks and limitations of bioinformatics algorithms and the necessity of experimental approaches for miRNA target identification. This article is part of a Special Issue entitled 'Non-coding RNAs'. ..
- Glucocorticoid insensitivity at the hypoxic blood-brain barrier can be reversed by inhibition of the proteasomeChristoph Kleinschnitz
University of Wurzburg, Department of Neurology, Josef Schneider Strasse 11, D 97080 Wurzburg, Germany
Stroke 42:1081-9. 2011..The reasons for this discrepancy are unresolved...
- Circulating endothelial progenitor cells in patients with Eisenmenger syndrome and idiopathic pulmonary arterial hypertensionGerhard Paul Diller
Adult Congenital Heart Centre and Centre for Pulmonary Hypertension, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK
Circulation 117:3020-30. 2008..We speculated that PAH patients are deficient in circulating endothelial progenitor cells (EPCs), potentially contributing to endothelial dysfunction and disease progression...
- Mechanistic role of cytochrome P450 monooxygenases in oxidized low-density lipoprotein-induced vascular injury: therapy through LOX-1 receptor antagonism?Thomas Thum
Center of Drug Research and Medical Biotechnology, Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany
Circ Res 94:e1-13. 2004..Therapy of endothelial dysfunction through LOX-1 receptor antagonism will be an interesting avenue to explore. The full text of this article is available online at http://www.circresaha.org...
- Letter by Thum et al regarding article, "Oxidant stress impairs in vivo reendothelialization capacity of endothelial progenitor cells from patients with type 2 diabetes mellitus: restoration by the peroxisome proliferator-activated receptor-gamma agoThomas Thum
Circulation 117:e185; author reply e186. 2008
- Mechanisms underlying recoupling of eNOS by HMG-CoA reductase inhibition in a rat model of streptozotocin-induced diabetes mellitusPhilip Wenzel
Second Medical Clinic, Department of Cardiology and Angiology, Johannes Gutenberg University, Langenbeckstrasse 1, 55131 Mainz, Germany
Atherosclerosis 198:65-76. 2008....
- Growth hormone induces eNOS expression and nitric oxide release in a cultured human endothelial cell lineThomas Thum
Fraunhofer Institute of Toxicology and Experimental Medicine ITEM, Drug Research and Medical Biotechnology, 30625, Hannover, Germany
FEBS Lett 555:567-71. 2003..The enhanced eNOS gene/protein expression and enzyme activity correlate well. Our findings are suggestive for a novel role of growth hormone in endothelial biology, and particularly NO production...
- Mobilization of bone marrow-derived stem cells after myocardial infarction and left ventricular function: simply effects of optimized drug treatment?Thomas Thum
Eur Heart J 26:1685; author reply 1685-6. 2005
- Verapamil: metabolism in cultures of primary human coronary arterial endothelial cellsJurgen Borlak
Center for Drug Research and Medical Biotechnology, Fraunhofer Institute of Toxicology and Experimental Medicine, Nicolai Fuchs Str 1, D 30659 Hannover, Germany
Drug Metab Dispos 31:888-91. 2003....
- Accurate quantification of dimethylamine (DMA) in human urine by gas chromatography-mass spectrometry as pentafluorobenzamide derivative: evaluation of the relationship between DMA and its precursor asymmetric dimethylarginine (ADMA) in health and diseaseDimitrios Tsikas
Institut fur Klinische Pharmakologie, Medizinische Hochschule Hannover, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
J Chromatogr B Analyt Technol Biomed Life Sci 851:229-39. 2007..17+/-4.2) being insignificantly lower (P=0.46). Between urinary DMA and ADMA there was a positive correlation (R=0.6655, P<0.0001) in coronary artery disease, but no correlation (R=0.27339) was found in end-stage liver disease...
- Sports or statins for atheroprotection? New insight from Kruppel-like factor 2Thomas Thum
Cardiovasc Res 72:193-5. 2006
- Tilarginine in patients with acute myocardial infarction and cardiogenic shockJan T Kielstein
JAMA 298:971; author reply 972-3. 2007
- GC-MS assay for hepatic DDAH activity in diabetic and non-diabetic rats by measuring dimethylamine (DMA) formed from asymmetric dimethylarginine (ADMA): evaluation of the importance of S-nitrosothiols as inhibitors of DDAH activity in vitro and in vivo inKristine Chobanyan
Institute of Clinical Pharmacology, Hannover Medical School, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
J Chromatogr B Analyt Technol Biomed Life Sci 858:32-41. 2007..The GC-MS assay reported here should be suitable to probe for DDAH activity in various disease models...
- Testosterone, cytochrome P450, and cardiac hypertrophyThomas Thum
Center of Drug Research and Medical Biotechnology, Fraunhofer Institute of Toxicology and Aerosol Research, Hannover, Germany
FASEB J 16:1537-49. 2002..We show alpha-MHC to be significantly repressed in cardiac hypertrophy and restored to normal on testosterone supplementation. We conclude that heart-specific steroid metabolism is of critical importance in cardiac hypertrophy..
- Hallmarks of ion channel gene expression in end-stage heart failureJurgen Borlak
Fraunhofer Institute of Toxicology and Experimental Medicine, Center for Drug Research and Medical Biotechnology, 30625 Hannover, Germany
FASEB J 17:1592-608. 2003..Overall, the reversal of repressed ion channel gene expression in patients with implanted assist devices exemplifies the complex interactions between pressure load/stretch force and heart-specific gene expression...
- A rapid and simple CYP2D6 genotyping assay--case study with the analgetic tramadolJurgen Borlak
Fraunhofer Institute of Toxicology and Experimental Mecicine, Center of Drug Research and Medical Biotechnology, Hannover, Germany
Metabolism 52:1439-43. 2003..Our assay can be used reliably in clinical pharmacology studies and may be used for dose adjustment...
- Detection of early signals of hepatotoxicity by gene expression profiling studies with cultures of metabolically competent human hepatocytesThomas Thum
Fraunhofer Institute of Toxicology and Experimental Medicine, Centre for Drug Research and Medical Biotechnology, Nikolai Fuchs Str 1, 30625, Hannover, Germany
Arch Toxicol 82:89-101. 2008..In conclusion, xenobiotic induced hepatotoxicity may arise via several mechanisms and gene expression profiling helps to pinpoint location and pathways perturbed by drugs and chemicals...
- Androgen metabolism in thymus of fetal and adult ratsJurgen Borlak
Fraunhofer Institute of Toxicology and Experimental Medicine, Center for Drug Research and Medical Biotechnology, Nikolai Fuchs Str 1, D 30625 Hannover, Germany
Drug Metab Dispos 32:675-9. 2004..Changes of the underlying steroid-metabolizing enzyme systems may aid in understanding the role of androgens in altering biological functions of the thymus...
- Clostridium difficile toxin A induces expression of the stress-induced early gene product RhoBRalf Gerhard
Institute of Toxicology, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
J Biol Chem 280:1499-505. 2005....
- Cardiac dissonance without conductors: how dicer depletion provokes chaos in the heartThomas Thum
Circulation 118:1524-7. 2008
- Aroclor 1254 modulates gene expression of nuclear transcription factors: implications for albumin gene transcription and protein synthesis in rat hepatocyte culturesJurgen Borlak
Center for Drug Research and Medical Biotechnology, Fraunhofer Institute of Toxicology and Aerosol Research, Germany
Toxicol Appl Pharmacol 181:79-88. 2002....
- Obesity and risk of myocardial infarction: the INTERHEART studyThomas Thum
Lancet 367:1051-2; author reply 1054. 2006
- Expression of xenobiotic metabolizing enzymes in different lung compartments of smokers and nonsmokersThomas Thum
Drug Research and Medical Biotechnology, Fraunhofer Instituteof technology and Experimental Medicien, Hannover, Germany
Environ Health Perspect 114:1655-61. 2006..Cytochrome P450 monooxygenases (CYP) play an important role in the defense against inhaled toxicants, and expression of CYP enzymes may differ among various lung cells and tissue compartments...
- Verapamil: new insight into the molecular mechanism of drug oxidation in the human heartMarkus Walles
Fraunhofer Institute of Toxicology and Aerosol Research, Center of Drug Research and Medical Biotechnology, Hannover, Germany
J Chromatogr A 970:117-30. 2002..A fine example of the considerable metabolic competence of human heart is the formation of M1-M4, e.g. dealkylverapamil, norverapamil and isomers of O-demethylverapamil, which were believed to be exclusively produced by the liver...