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Involvement of endoplasmic reticulum stress-associated apoptosis in a heart failure model induced by chronic myocardial ischemia

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Apoptosis plays a critical role in the pathogenesis of chronic myocardial ischemia (CMI) and heart failure (HF). Endoplasmic reticulum stress (ERS) is one of the newly defined signaling pathways which initiate apoptosis. Previous studies have shown that ERS-associated apoptosis is involved in the pathogenesis of HF induced by pressure-overload and acute myocardial infarction. Also, inĀ vitro experiments have proved that ischemia is a strong stimulus of ERS. This study aimed to demonstrate whether ERS-associated apoptosis is involved in the pathogenesis of CMI-induced HF. We established a HF model induced by CMI in mini pigs via placement of an ameroid constrictor around the proximal anterior descending branch of the left coronary artery (LAD). Furthermore, we used myocardial perfusion imaging, echocardiographic and hemodynamic measurements, hematoxylin-eosin staining, and terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling staining to identify the existence of myocardial ischemia and cardiac dysfunction and of enhanced apoptosis in the ischemic heart. We performed immunohistochemistry, Western blot, and real-time PCR to analyze the hallmark of ERS glucose-regulated protein 78 (GRP78). The ERS-associated apoptotic pathways, CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, and c-Jun NH2-terminal kinaseĀ 1 (JNK1) were also examined. We found that all three of these pathways were activated and that GRP78 protein and mRNA levels were significantly enhanced in the myocardium of HF mini pigs induced by CMI. These results suggest that ERS is present in the CMI-induced HF pig model, and that ERS-associated apoptosis is involved in the pathophysiology of HF induced by CMI.
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Document Type: Research Article

Affiliations: 1: First Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, P.R. China 2: 28 Fuxing Road, First Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing 100853, P.R. China

Publication date: January 1, 2011

More about this publication?
  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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