Interplay of angiotensin II and angiotensin(1-7) in the regulation of matrix metalloproteinases of human cardiocytes

Chun Hsu Pan, Cheng Hao Wen, Chih Sheng Lin

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Angiotensin II (Ang II) is a critical effector in the renin-angiotensin system (RAS), which modulates cardiovascular homeostasis, and the matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) related metabolism of extracellular matrix (ECM). Angiotensin(1-7) [Ang(1-7)] is another bioactive peptide in the RAS and is considered to have opposite effects to Ang II. However, the modulation of MMPs and TIMPs by Ang(1-7) is largely unclear in cardiocytes, and the antagonistic effects of Ang(1-7) on Ang II-mediated expression of MMPs and TIMPs have yet to be identified. In the present study, we examined the transcript expression of MMPs and TIMPs in human cardiac fibroblasts (HCF) and myocytes (HCM) after Ang II or Ang(1-7) stimulation, and analysed the antagonistic effects of Ang(1-7) to Ang II. The results show that Ang II decreased transcript expression of MMP-1, MMP-2, TIMP-1, TIMP-2 and TIMP-3, but upregulated MMP-9 expression in the HCF cells. Transcript expression of MMP-9 and TIMP-2 was downregulated by Ang(1-7) in the same cells. In the HCM cells, Ang II induced MMP-1 and MMP-9 overexpression but MMP-2 was downregulated. All of the examined MMPs and TIMPs, except MMP-9, were markedly decreased by Ang(1-7). In the studies of antagonistic effects of Ang(1-7) to Ang II, Ang(1-7) counteracted the effects of Ang II-mediated regulation on MMP-9 and TIMP-1 in the HCF cells compared with the control group. The regulations of all examined MMPs by Ang II were reversed to basal expression by Ang(1-7) in the HCM cells. Our results suggest that Ang(1-7) and Ang II have opposite and antagonistic effects on regulation of transcription of MMPs and TIMPs in primary cultures of human cardiocytes. These effects lead to increased ratios of MMPs to TIMPs after Ang II stimulation and decreased ratios of MMPs to TIMPs after Ang(1-7) stimulation; effects which may partly depend of the type of cardiac cells. These results suggest a potential role for Ang(1-7) in attenuatating cardiac damage in Ang II-induced ECM remodelling.

Original languageEnglish
Pages (from-to)599-612
Number of pages14
JournalExperimental Physiology
Issue number5
Publication statusPublished - May 2008
Externally publishedYes


ASJC Scopus subject areas

  • Physiology

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