Interplay of angiotensin II and angiotensin 1–7 in the regulations of matrix metalloproteinases of human cardiocytes

Angiotenisn 1–7 (Ang 1–7) is considered to play an opposing role to angiotensin II (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. We examined the mRNA expression of MMPs and TIMPs in human cardiac fibroblasts (HCF) and cardiac myocytes (HCM) stimulated by Ang II or Ang 1–7, and analyzed the antagonistic effects of Ang 1–7 to Ang II. Ang II decreased transcript expression of MMP‐1, MMP‐2, TIMP‐1, TIMP‐2 and TIMP‐3, but downregulated MMP‐9 expression in the HCF cells. Transcript expression of MMP‐9 and TIMP‐2 were downregulated by Ang 1–7 in the cells. In the HCM cells, Ang II induced MMP‐1 and MMP‐9 expression, but all of examined MMPs and TIMPs, except MMP‐9, were markedly decreased by Ang 1–7. Ang 1–7 could counteract the effects of Ang II‐mediated regulations on MMP‐1, MMP‐9 and TIMP‐1 in the HCF cells. The regulations of all examined MMPs by Ang II were reversed to basal expression by Ang 1–7 in the HCM cells. Opposite regulation in the examined MMPs and TIMPs expression was found between Ang II and Ang 1–7, and the antagonistic effects of Ang 1–7 to Ang II were also identified. These results might raise a potential role of Ang 1–7 to attenuate Ang II‐induced ECM remodeling in heart. This work was supported by National Science Council (NSC 95‐2313‐B‐009‐002‐MY3), Taiwan.