1. Myocardial insulin-like growth factor-I gene expression during recovery from heart failure after combined left ventricular assist device and clenbuterol therapy.
- Author
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Barton PJ, Felkin LE, Birks EJ, Cullen ME, Banner NR, Grindle S, Hall JL, Miller LW, and Yacoub MH
- Subjects
- Adrenergic beta-2 Receptor Agonists, Cardiomyopathy, Dilated complications, Cardiomyopathy, Dilated surgery, Chemokine CXCL12, Chemokines, CXC biosynthesis, Chemokines, CXC genetics, Combined Modality Therapy, Convalescence, Follow-Up Studies, Gene Expression Profiling, Heart Failure drug therapy, Heart Failure etiology, Heart Failure genetics, Heart Failure surgery, 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 genetics, Insulin-Like Growth Factor II biosynthesis, Insulin-Like Growth Factor II genetics, Myocardium metabolism, Oligonucleotide Array Sequence Analysis, RNA, Messenger biosynthesis, Regeneration, Reverse Transcriptase Polymerase Chain Reaction, Stroke Volume, Ventricular Remodeling genetics, Adrenergic beta-Agonists therapeutic use, Clenbuterol therapeutic use, Heart Failure metabolism, Heart-Assist Devices, Insulin-Like Growth Factor I biosynthesis
- Abstract
Background: 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., Methods and Results: 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., Conclusions: 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.
- Published
- 2005
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