Open Access

Alamandine attenuates long‑term hypertension‑induced cardiac fibrosis independent of blood pressure

  • Authors:
    • Lan Wang
    • Chi Liu
    • Xiru Chen
    • Peng Li
  • View Affiliations

  • Published online on: April 15, 2019     https://doi.org/10.3892/mmr.2019.10167
  • Pages: 4553-4560
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cardiac fibrosis secondary to long‑term hypertension is known to promote cardiac dysfunction; however, few therapeutic agents are available for the treatment of this condition in clinical practice. The heptapeptide alamandine (Ala) has recently been identified as a component of the renin‑angiotensin system (RAS), which exerts a protective effect against cardiac hypertrophy; however, it is unknown whether Ala may also be useful for the treatment of cardiac fibrosis. In the present study, the potential therapeutic effects of Ala on long‑term hypertension‑induced cardiac fibrosis were investigated in an aged, spontaneous hypertensive rat model. Weekly blood pressure (BP) measurements revealed that daily Ala treatment significantly decreased the systolic, diastolic and mean arterial BP compared with the control. Of note, the observed reduction in BP in Ala‑treated animals markedly differed to that observed in rats treated with hydralazine (Hyd). Echocardiography further demonstrated that Ala treatment decreased the ratio of left ventricle mass to body weight, and alleviated structural and functional parameters associated with cardiac fibrosis, including left ventricular volume, ejection fraction and fractional shortening compared with the control and Hyd‑treated groups. Furthermore, Ala deceased the density of cardiac fibrosis, as assessed by Masson and Sirius red staining; reduced expression of fibrotic proteins, including connective tissue growth factor, collagen I (COL1A1) and matrix metalloproteinase 9, was also observed. In addition, Ala treatment further decreased the expression of angiotensin II‑induced fibrotic markers at the mRNA and protein levels in cultured cardiac fibroblasts; Ala‑mediated inhibition of COL1A1 expression and Akt phosphorylation was inhibited via the Mas‑related G protein receptor antagonist, PD123319. Collectively, the findings of the present study suggest that Ala is an effective anti‑hypertensive peptide that can attenuate cardiac dysfunction and fibrosis induced by chronic hypertension, independent of BP.

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Copy and paste a formatted citation
APA
Wang, L., Liu, C., Chen, X., & Li, P. (2019). Alamandine attenuates long‑term hypertension‑induced cardiac fibrosis independent of blood pressure. Molecular Medicine Reports, 19, 4553-4560. https://doi.org/10.3892/mmr.2019.10167
MLA
Wang, L., Liu, C., Chen, X., Li, P."Alamandine attenuates long‑term hypertension‑induced cardiac fibrosis independent of blood pressure". Molecular Medicine Reports 19.6 (2019): 4553-4560.
Chicago
Wang, L., Liu, C., Chen, X., Li, P."Alamandine attenuates long‑term hypertension‑induced cardiac fibrosis independent of blood pressure". Molecular Medicine Reports 19, no. 6 (2019): 4553-4560. https://doi.org/10.3892/mmr.2019.10167