The ACE2-Ang (1-7)-Mas receptor axis attenuates cardiac remodeling and fibrosis in post-myocardial infarction

Wang,Juan; He,Wen; Guo,Liping; Zhang,Yin; Li,Hui; Han,Suxia; Shen,Difei

doi:10.3892/mmr.2017.6848

The ACE2-Ang (1-7)-Mas receptor axis attenuates cardiac remodeling and fibrosis in post-myocardial infarction

Authors:
- Juan Wang
- Wen He
- Liping Guo
- Yin Zhang
- Hui Li
- Suxia Han
- Difei Shen
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Affiliations: Department of Cardiology, The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830001, P.R. China, Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830001, P.R. China, Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Published online on: June 23, 2017 https://doi.org/10.3892/mmr.2017.6848
Pages: 1973-1981
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Myocardial remodeling serves an important role in the pathophysiology of coronary heart disease. The angiotensin-converting enzyme (ACE)2-angiotensin-(1-7) [Ang (1‑7)]‑Mas receptor (MasR) axis is a key regulator in myocardial remodeling and development of heart failure. To investigate how ACE2‑Ang‑(1‑7)‑MasR axis function on myocardial remodeling and cardiac fibrosis in post‑myocardial infarction (MI), male Sprague‑Dawley rats (weight, 200±20 g) were used to establish the model of myocardial infarction by ligating the left coronary artery. The present study suggests that telmisartan (Tel) and olmesartan (Olm) (5 mg/kg/d) can inhibit myocardial remodeling of post‑myocardial infarction through the ACE2‑Ang (1‑7)‑MasR pathway. Administration of Tel or Olm was demonstrated to significantly inhibit collagen deposition using Masson staining. In addition, telmisartan and olmesartan was indicated to antagonize angiotensin II (Ang II) and upregulate ACE2, MasR, Ang (1‑7) expression in myocardial tissue using immunoassay and ELISA test, and the effect of Olm was more marked than that of Tel at the same dosage. Simultaneously, compared with the MI or Sham group, the mRNA and protein expression of ACE2, Ang II and MasR in myocardial tissue demonstrated a remarkable increase in the Olm group, when compared with the Tel group. Taken together, our data demonstrated that ACE2‑Ang (1‑7)‑MasR axis may present a potential protective role in the development of myocardial remodeling and may provide a new target for drug development of cardiac fibrosis. In conclusion, Olm is superior to Tel in inhibiting myocardial local Ang II level reducing myocardial collagen deposition and improving myocardial remodeling by upregulating the expression of ACE2, Ang (1‑7) and MasR.

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