Ablation of C/EBP homologous protein increases the acute phase mortality and doesn't attenuate cardiac remodeling in mice with myocardial infarction
| Autor: | Masafumi Kitakaze, Qingman Li, Jiahe Xie, Xiajun Zhang, Guangjin Luo, Yulin Liao, Xiaobo Huang, Jingwen Zhang, Liang Shen |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
genetic structures Ischemia Myocardial Infarction Biophysics Infarction Gene Expression Heart failure Apoptosis CHOP Biochemistry C/EBP homologous protein Mice hemic and lymphatic diseases Internal medicine medicine Animals Myocytes Cardiac Myocardial infarction Molecular Biology Ultrasonography Pressure overload Mice Knockout Ejection fraction Ventricular Remodeling business.industry Myocardium Hemodynamics Cell Biology medicine.disease Survival Analysis Disease Models Animal Cardiology Myocardial fibrosis business Gene Deletion Transcription Factor CHOP |
| Zdroj: | Biochemical and Biophysical Research Communications. 464(1):201-207 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2015.06.117 |
| Popis: | Endoplasmic reticulum stress is a proapoptotic and profibrotic stimulus. Ablation of C/EBP homologous protein (CHOP) is reported to reverse cardiac dysfunction by attenuating cardiac endoplasmic reticulum stress in mice with pressure overload or ischemia/reperfusion, but it is unclear whether loss of CHOP also inhibits cardiac remodeling induced by permanent-infarction. In mice with permanent ligation of left coronary artery, we found that ablation of CHOP increased the acute phase mortality. For the mice survived to 4 weeks, left ventricular anterior (LV) wall thickness was larger in CHOP knockout mice than in the wildtype littermates, while no difference was noted on posterior wall thickness, LV dimensions, LV fractional shortening and ejection fraction. Similarly, invasive assessment of LV hemodynamics, morphological analysis of heart and lung weight indexes, myocardial fibrosis and TUNEL-assessed apoptosis showed no significant differences between CHOP knockout mice and their wildtype ones, while in mice with ischemia for 45 min and reperfusion for 1 week, myocardial fibrosis and apoptosis in the infarct area were significantly attenuated in CHOP knockout mice. These findings indicate that ablation of CHOP doesn't ameliorate cardiac remodeling induced by permanent-myocardial infarction, which implicates that early reperfusion is a prerequisite for ischemic myocardium to benefit from CHOP inhibition. |
| Databáze: | OpenAIRE |
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