title: 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.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Guangjin
authors.initials: G
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Qingman
authors.initials: Q
authors.lastname: Li
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xiajun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jiahe
authors.initials: J
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Cardiovascular Division of the Department of Medicine, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: chw47922@163.com.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: liao18@msn.com.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liao
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D017353:Gene Deletion; D015870:Gene Expression; D006439:Hemodynamics; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D016019:Survival Analysis; D051742:Transcription Factor CHOP / Q000172:deficiency / Q000235:genetics*; D014463:Ultrasonography; D020257:Ventricular Remodeling
chemical_list: C497250:Ddit3 protein, mouse; D051742:Transcription Factor CHOP
keywords: C/EBP homologous protein; Heart failure; Myocardial infarction