Circulation (New York, N.Y.), 2005-08, Vol.112 (9), p.I46-I50
2005
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- Autor(en) / Beteiligte
- Titel
- Myocardial insulin-like growth factor-I gene expression during recovery from heart failure after combined left ventricular assist device and clenbuterol therapy
- Ist Teil von
- Circulation (New York, N.Y.), 2005-08, Vol.112 (9), p.I46-I50
- Ort / Verlag
- Hagerstown, MD: Lippincott Williams & Wilkins
- Erscheinungsjahr
- 2005
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Patients who undergo mechanical support with a left ventricular assist device (LVAD) exhibit reverse remodeling and in some cases recover from heart failure. We have developed a combination therapy using LVAD support combined with pharmacological therapy to maximize reverse remodeling, followed by the beta2 adrenergic agonist clenbuterol. We recently found that clenbuterol induces insulin-like growth factor I (IGF-I) in cardiac myocytes in vitro. The purpose of this study is to examine IGF-I expression in recovery patients after combination therapy. Myocardial mRNA levels were determined by real-time quantitative polymerase chain reaction in 12 recovery patients (at LVAD implantation, explantation, and 1 year after explantation). IGF-I mRNA was elevated at the time of LVAD explantation relative to donors, with 2 groups distinguishable: Those with low IGF-I mRNA at implantation who showed significant increase during recovery and those with high IGF-I mRNA at implantation who remained high. Levels returned to normal by 1 year after explantation. Microarray analysis of implantation and explantation samples of recovery patients further revealed elevated IGF-II and IGF binding proteins IGFBP4 and IGFBP6. IGF-I levels correlated with stromal cell-derived factor mRNA measured both in LVAD patients and in a wider cohort of heart failure patients. The data suggest involvement of elevated myocardial IGF-I mRNA in recovery. IGF-I may act to limit atrophy and apoptosis during reverse remodeling and to promote repair and regeneration in concert with stromal cell derived factor.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0009-7322eISSN: 1524-4539DOI: 10.1161/01.circulationaha.105.525873Titel-ID: cdi_proquest_miscellaneous_68570506
- Format
- –
- Schlagworte
- Adrenergic beta-2 Receptor Agonists, Adrenergic beta-Agonists - therapeutic use, Biological and medical sciences, Blood and lymphatic vessels, Blood vessels and receptors, Blood. Blood coagulation. Reticuloendothelial system, Cardiology. Vascular system, Cardiomyopathy, Dilated - complications, Cardiomyopathy, Dilated - surgery, Chemokine CXCL12, Chemokines, CXC - biosynthesis, Chemokines, CXC - genetics, Clenbuterol - therapeutic use, Combined Modality Therapy, Convalescence, Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous, Follow-Up Studies, Fundamental and applied biological sciences. Psychology, Gene Expression Profiling, Heart Failure - drug therapy, Heart Failure - etiology, Heart Failure - genetics, Heart Failure - metabolism, Heart Failure - surgery, Heart-Assist Devices, Humans, Insulin-Like Growth Factor Binding Protein 4 - biosynthesis, Insulin-Like Growth Factor Binding Protein 4 - genetics, Insulin-Like Growth Factor Binding Protein 6 - biosynthesis, Insulin-Like Growth Factor Binding Protein 6 - genetics, Insulin-Like Growth Factor I - biosynthesis, Insulin-Like Growth Factor I - genetics, Insulin-Like Growth Factor II - biosynthesis, Insulin-Like Growth Factor II - genetics, Medical sciences, Myocardium - metabolism, Oligonucleotide Array Sequence Analysis, Pharmacology. Drug treatments, Regeneration, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger - biosynthesis, Stroke Volume, Ventricular Remodeling - genetics, Vertebrates: cardiovascular system