Ablation of C/EBP homologous protein increases the acute phase mortality and doesn't attenuate cardiac remodeling in mice with myocardial infarction.

Abstract

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.

• Authors: Guangjin Luo, Qingman Li, Xiajun Zhang, Liang Shen, Jiahe Xie, Jingwen Zhang, Masafumi Kitakaze, Xiaobo Huang, Yulin Liao
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 464 Issue 1 Pg. 201-7 (Aug 14 2015) ISSN: 1090-2104 [Electronic] United States
• PMID: 26111448 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Ddit3 protein, mouse
• Transcription Factor CHOP

Topics

• Animals
• Apoptosis
• Disease Models, Animal
• Gene Deletion
• Gene Expression
• Hemodynamics
• Mice
• Mice, Knockout
• Myocardial Infarction (diagnostic imaging, genetics, mortality, pathology)
• Myocardium (metabolism, pathology)
• Myocytes, Cardiac (metabolism, pathology)
• Survival Analysis
• Transcription Factor CHOP (deficiency, genetics)
• Ultrasonography
• Ventricular Remodeling