Received December 20, 2007
Revised January 29, 2008
Accepted after revision February 18, 2008
Heart/Cardiac Muscle [240]
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Interplay of angiotensin II and angiotensin 1-7 in the regulations of matrix metalloproteinases of human cardiocytes
Chun-Hsu Pan 1,
Cheng-Hao Wen 1,
Chih-Sheng Lin 1*
1 National Chiao Tung University
* To whom correspondence should be addressed. E-mail: lincs{at}mail.nctu.edu.tw.
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Abstract |
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Angiotensin II (Ang II) is a critical effector in renin-angiotensin system (RAS), which modulates the cardiovascular homeostasis, and matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) related metabolism of extracellular matrix (ECM). Angiotenisn 1-7 (Ang 1-7) is also a bioactive peptide in RAS, which is considered to play a role of opposing effects to Ang II. However, the modulation of MMPs and TIMPs by Ang 1-7 is largely unclear in cardiocytes, and the counteractive effects of Ang 1-7 on Ang II-mediated MMPs and TIMPs expression need to be identified. In the present study, we examined the transcript expression of MMPs and TIMPs in human cardiac fibroblasts (HCF) and cardiac myocytes (HCM) after Ang II or Ang 1-7 stimulation, and analyzed 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 were 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 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 regulations on MMP-9 and TIMP-1 in the HCF cells as 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 MMPs and TIMPs transcription in primary cultures of human cardiocytes. These effects lead to increased MMPs/TIMPs ratios after Ang II stimulation and decreased MMPs/TIMPs ratios after Ang 1-7 stimulation, which effects partial may depend of the type of cardiac cells. These results might raise a potential role of Ang 1-7 to attenuate the heart damage in Ang II-induced ECM remodeling.
Key Words:
Angiotensin, Cardiac cell, Extracellular matrix
