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• W3148481552 abstract "Endoplasmic reticulum stress(ERS) is an adaptive process in response to circumstantial changes,but excessive and/or prolonged ERS can induce cell apoptosis.C/EBP homologous protein(CHOP) is a very important marker participating in ERS-associated cell apoptosis,while the role of the myocyte apoptosis induced by CHOP remains unclear in the development of hypertrophy.The present study aimed to investigate the effect of CHOP-mediated ERS-associated apoptosis on myocardial hypertrophy induced by abdominal aortic constriction in rats.Healthy male Wistar rats were randomly divided into model group(n=45) and control group(n=40).The rats in model group received abdominal aortic constriction.Hemodynamic changes,whole heart weight/body weight(HW/BW) and left ventricular weight/body weight(LVW/BW) were measured on 1 d,3 d,7 d,14 d and 28 d after surgery,respectively.The mRNA expression of glucose-regulated protein 78(GRP78),calreticulin(CRT) and CHOP,which are important markers of ERS,were detected by RT-PCR,and Western blot was used to assess the protein level of GRP78,CRT,CHOP,and apoptosis-associated proteins,Bax and Bcl-2.The results obtained were as follows.Compared with control group,the blood pressure,LVW/BW,and HW/BW of rats in model group increased significantly and cardiac function enhanced compensatively on 7 d after surgery,and increased progressively during the experiment.As early as 1 d after surgery,the mRNA level of CRT in model group increased by 136%(P0.01) compared with control,while the protein expression increased by 69.2% on 7 d after surgery(P0.01).Both mRNA and protein expression of GRP78 increased by 20% and 186%(P0.01) respectively on 7 d after surgery,and the expression sustained high level during the experiment afterwards.Correlation analysis indicated a positive correlation between +dp/dtmax and CRT protein expression(r=0.780,P0.01) as well as GRP78 protein expression(r=0.694,P0.01).Prolonged ERS triggered myocyte apoptosis,as both the mRNA and protein level of CHOP in model group increased by 22.2%(P0.01) and 76.0%(P0.01) respectively compared with control on 7 d after hypertrophy(14 d after surgery),and meanwhile,the protein expression of pro-apoptotic Bax increased by 41.1%(P0.01) and anti-apoptotic Bcl-2 protein expression decreased by 25.5%(P0.01).Correlation analysis indicated a positive correlation between CHOP and Bax expression(r=0.654,P0.01),and a negative correlation between CHOP and Bcl-2 expression(r=-0.671,P0.01).These results suggest that abdominal aortic constriction induces a significant up-regulation in ER molecular chaperones at early stage of post-surgery,indicating that ERS response is activated in the rat heart;while prolonged ERS could lead to myocyte apoptosis,and CHOP-mediated ERS-associated apoptosis may contribute to myocardial hypertrophy.We speculate that cell apoptosis may take part in the regulation of myocardial hypertrophy and heart failure,and determine the progression of decompensated hypertrophy." @default.
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• W3148481552 date "2009-01-01" @default.
• W3148481552 modified "2023-09-23" @default.
• W3148481552 title "C/EBP homologous protein-mediated endoplasmic reticulum stress-related apoptosis pathway is involved in abdominal aortic constriction-induced myocar-dium hypertrophy in rats" @default.
• W3148481552 hasPublicationYear "2009" @default.
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