CHF1/Hey2 Promotes Physiological Hypertrophy in Response to Pressure Overload through Selective Repression and Activation of Specific Transcriptional Pathways
| Autor: | Yonggang Liu, Fan Xiang, Ronglih Liao, Man Yu, Theodor K. Bammler, Michael T. Chin, Richard P. Beyer, Darragh Cullen, Yuxin Li |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Genetically modified mouse
medicine.medical_specialty Transcription Genetic Transgene Molecular Sequence Data Apoptosis Blood Pressure Cardiomegaly Mice Transgenic Biology Biochemistry Muscle hypertrophy Mice Fibrosis Internal medicine Basic Helix-Loop-Helix Transcription Factors In Situ Nick-End Labeling Genetics medicine Animals Myocytes Cardiac Molecular Biology Cells Cultured Pressure overload TUNEL assay Myocardium Original Articles Microarray Analysis medicine.disease Repressor Proteins Endocrinology Gene Expression Regulation Heart failure Molecular Medicine Signal Transduction Biotechnology |
| Zdroj: | OMICS: A Journal of Integrative Biology. 13:501-511 |
| ISSN: | 1557-8100 1536-2310 |
| Popis: | We have previously found that CHF1/Hey2 prevents the development of phenylephrine-induced cardiac hypertrophy. To determine the role of CHF1/Hey2 in pressure overload hypertrophy, we performed ascending aortic banding on wild-type and transgenic mice overexpressing CHF1/Hey2 in the myocardium. We found that both wild-type and transgenic mice developed increased ventricular weight to body weight ratios 1 week after aortic banding. Wild-type mice also developed decreased fractional shortening after 1 week when compared to preoperative echocardiograms and sham-operated controls. Transgenic mice, in comparison, demonstrated preserved fractional shortening. Histological examination of explanted heart tissue demonstrated extensive fibrosis in wild-type hearts, but minimal fibrosis in transgenic hearts. TUNEL staining demonstrated increased apoptosis in the wild-type hearts but not in the transgenic hearts. Exposure of cultured neonatal myocytes from wild-type and transgenic animals to hydrogen peroxide, a potent inducer of apoptosis, demonstrated increased apoptosis in the wild-type cells. Gene Set Analysis of microarray data from wild-type and transgenic hearts 1 week after banding revealed suppression and activation of multiple pathways involving apoptosis, cell signaling, and biosynthesis. These findings demonstrate that CHF1/Hey2 promotes physiological over pathological hypertrophy through suppression of apoptosis and regulation of multiple transcriptional pathways. These findings also suggest that CHF1/Hey2 and its downstream pathways provide a variety of targets for novel heart failure drug discovery, and that genetic polymorphisms in CHF1/Hey2 may affect susceptibility to hypertrophy and heart failure. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|