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

  • Authors:
    • Wei Xin
    • Xiaoying Li
    • Xiaochun Lu
    • Kun Niu
    • Jimei Cai
  • View Affiliations

  • Published online on: February 3, 2011     https://doi.org/10.3892/ijmm.2011.612
  • Pages: 503-509
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Abstract

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, in 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 kinase 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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April 2011
Volume 27 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Copy and paste a formatted citation
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Spandidos Publications style
Xin W, Li X, Lu X, Niu K and Cai J: Involvement of endoplasmic reticulum stress-associated apoptosis in a heart failure model induced by chronic myocardial ischemia. Int J Mol Med 27: 503-509, 2011.
APA
Xin, W., Li, X., Lu, X., Niu, K., & Cai, J. (2011). Involvement of endoplasmic reticulum stress-associated apoptosis in a heart failure model induced by chronic myocardial ischemia. International Journal of Molecular Medicine, 27, 503-509. https://doi.org/10.3892/ijmm.2011.612
MLA
Xin, W., Li, X., Lu, X., Niu, K., Cai, J."Involvement of endoplasmic reticulum stress-associated apoptosis in a heart failure model induced by chronic myocardial ischemia". International Journal of Molecular Medicine 27.4 (2011): 503-509.
Chicago
Xin, W., Li, X., Lu, X., Niu, K., Cai, J."Involvement of endoplasmic reticulum stress-associated apoptosis in a heart failure model induced by chronic myocardial ischemia". International Journal of Molecular Medicine 27, no. 4 (2011): 503-509. https://doi.org/10.3892/ijmm.2011.612