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Imbalance of angiotensin-converting enzymes affects myocardial apoptosis during cardiac arrest induced by acute pulmonary embolism in a porcine model.
Int J Mol Med. 2019 Apr; 43(4):1575-1584.IJ

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.

Authors+Show Affiliations

Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.Department of Emergency Medicine, Beijing Chao‑Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.Department of Emergency Medicine, Beijing Chao‑Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.Department of Emergency Medicine, Beijing Chao‑Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.Department of Emergency Medicine, Beijing Chao‑Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.Department of Radiology, Beijing Chao‑Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30816437

Citation

Xiao, Hong-Li, et al. "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, vol. 43, no. 4, 2019, pp. 1575-1584.
Xiao HL, Zhao LX, Yang J, et al. Imbalance of angiotensin-converting enzymes affects myocardial apoptosis during cardiac arrest induced by acute pulmonary embolism in a porcine model. Int J Mol Med. 2019;43(4):1575-1584.
Xiao, H. L., Zhao, L. X., Yang, J., Tong, N., An, L., Liu, Q. T., Xie, M. R., & Li, C. S. (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(4), 1575-1584. https://doi.org/10.3892/ijmm.2019.4109
Xiao HL, et al. Imbalance of Angiotensin-converting Enzymes Affects Myocardial Apoptosis During Cardiac Arrest Induced By Acute Pulmonary Embolism in a Porcine Model. Int J Mol Med. 2019;43(4):1575-1584. PubMed PMID: 30816437.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Imbalance of angiotensin-converting enzymes affects myocardial apoptosis during cardiac arrest induced by acute pulmonary embolism in a porcine model. AU - Xiao,Hong-Li, AU - Zhao,Lian-Xing, AU - Yang,Jun, AU - Tong,Nan, AU - An,Le, AU - Liu,Qi-Tong, AU - Xie,Miao-Rong, AU - Li,Chun-Sheng, Y1 - 2019/02/26/ PY - 2017/05/13/received PY - 2019/01/15/accepted PY - 2019/3/1/pubmed PY - 2019/7/31/medline PY - 2019/3/1/entrez SP - 1575 EP - 1584 JF - International journal of molecular medicine JO - Int J Mol Med VL - 43 IS - 4 N2 - 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. SN - 1791-244X UR - https://www.unboundmedicine.com/medline/citation/30816437/Imbalance_of_angiotensin_converting_enzymes_affects_myocardial_apoptosis_during_cardiac_arrest_induced_by_acute_pulmonary_embolism_in_a_porcine_model_ L2 - http://www.spandidos-publications.com/ijmm/43/4/1575 DB - PRIME DP - Unbound Medicine ER -