Open Access

Imbalance of angiotensin-converting enzymes affects myocardial apoptosis during cardiac arrest induced by acute pulmonary embolism in a porcine model

  • Authors:
    • Hong‑Li Xiao
    • Lian‑Xing Zhao
    • Jun Yang
    • Nan Tong
    • Le An
    • Qi‑Tong Liu
    • Miao‑Rong Xie
    • Chun-Sheng Li
  • View Affiliations

  • Published online on: February 26, 2019     https://doi.org/10.3892/ijmm.2019.4109
  • Pages: 1575-1584
  • Copyright: © Xiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute pulmonary embolism (APE) with cardiac arrest (CA) is associated with a high mortality rate. Even upon return of the spontaneous circulation (ROSC), APE‑CA survivors are prone to myocardial cell apoptosis, a key cellular mechanism that induces heart failure. A recent study by our group discovered a post‑resuscitation imbalance in the serum angiotensin‑converting enzyme (ACE)2/ACE axis of the renin‑angiotensin system (RAS), as well as regressive cardiac function in a porcine model of APE‑CA. However, it has remained elusive how this imbalance in the ACE2/ACE axis affects myocardial cell apoptosis. In the present study, western blot and immunohistochemical analyses demonstrated that the RAS was only activated in the left myocardium, as evidenced by a decreased ACE2/ACE ratio following APE‑CA and ROSC, but not the right myocardium. Ultrastructural analysis confirmed myocardial apoptosis in the left and right myocardium. Furthermore, B‑cell lymphoma 2 (Bcl‑2)‑associated X protein (Bax) and caspase‑3 levels were elevated and Bcl‑2 levels were decreased in the left myocardium following APE‑CA and ROSC. Treatment with the ACE inhibitor captopril for 30 min after initiation of ROSC prevented the increase in Bax and the decrease in Bcl‑2 in the left myocardium compared with that in saline‑treated pigs. Captopril also inhibited the activation of extracellular signal‑regulated kinase (ERK)1/2 in the left myocardium. The results of the present study suggest that an imbalance in the ACE2/ACE axis has an important role in myocardial apoptosis following APE‑CA, which may be attributed to decreased ERK1/2 activation. In addition, it was indicated that captopril prevents apoptosis in the left myocardium after ROSC.
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April-2019
Volume 43 Issue 4

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

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Spandidos Publications style
Xiao HL, Zhao LX, Yang J, Tong N, An L, Liu QT, Xie MR and Li C: Imbalance of angiotensin-converting enzymes affects myocardial apoptosis during cardiac arrest induced by acute pulmonary embolism in a porcine model. Int J Mol Med 43: 1575-1584, 2019
APA
Xiao, H., Zhao, L., Yang, J., Tong, N., An, L., Liu, Q. ... Li, C. (2019). Imbalance of angiotensin-converting enzymes affects myocardial apoptosis during cardiac arrest induced by acute pulmonary embolism in a porcine model. International Journal of Molecular Medicine, 43, 1575-1584. https://doi.org/10.3892/ijmm.2019.4109
MLA
Xiao, H., Zhao, L., Yang, J., Tong, N., An, L., Liu, Q., Xie, M., Li, C."Imbalance of angiotensin-converting enzymes affects myocardial apoptosis during cardiac arrest induced by acute pulmonary embolism in a porcine model". International Journal of Molecular Medicine 43.4 (2019): 1575-1584.
Chicago
Xiao, H., Zhao, L., Yang, J., Tong, N., An, L., Liu, Q., Xie, M., Li, C."Imbalance of angiotensin-converting enzymes affects myocardial apoptosis during cardiac arrest induced by acute pulmonary embolism in a porcine model". International Journal of Molecular Medicine 43, no. 4 (2019): 1575-1584. https://doi.org/10.3892/ijmm.2019.4109