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Cell-specific and endothelium-dependent regulations of matrix metalloproteinase-2 in rat aorta

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Abstract

Chronic activation of angiotensin II (ANGII) and matrix metalloproteinase-2 (MMP-2) during hypertension contributes to increased aortic stiffness. We studied signalling mechanisms employed by ANGII in the regulation of latent (pro-) and active forms of MMP-2 in rat aortic endothelial and smooth muscle cells, along with isolated rat aorta. Using western blotting, we demonstrate that ANGII (1 µmol/L) significantly (P < 0.01) increases pro-MMP-2 protein expression after 8 h not only in endothelial and smooth muscle cells, but also in isolated rat aorta. We demonstrate that ANGII acts via AT1 receptor-activated cell-specific pathways. In endothelial cells, the JNK1/c-jun pathway is activated, whereas in smooth muscle cells, the JAK2/STAT3 pathway. Activation of JAK2/STAT3 pathway in response to ANGII was EGF receptor-dependent. Results obtained in cell culture are in agreement with the results obtained in isolated aorta. However, active MMP-2 was not found under cell culture conditions, whereas in isolated aorta, active MMP-2 was significantly (P < 0.05) increased after stimulation with ANGII, as detected by gelatine zymography. This increase of MMP-2 activity was not inhibited by blocking the pathways we identified to control pro-MMP-2 protein expression, but was abolished in the absence of endothelium. Our findings demonstrate that ANGII regulates pro-MMP-2 protein expression via cell-specific pathways in rat aorta. The endothelium may play an essential role in the activation of pro-MMP-2. These results may lead to new strategies for inhibiting MMP-2 expression and activity in distinct cell types of the aortic wall.

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Acknowledgments

This work was supported by a grant-in-aid from the Federal Ministry of Education and Research of Germany (BMBF) (Grant: 0315473A).

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Authors and Affiliations

  1. Medical Faculty Carl Gustav Carus, Department of Physiology, TU Dresden, Fetscherstr. 74, Dresden, Germany

    Irakli Kopaliani, Melanie Martin, Birgit Zatschler, Katrin Bortlik, Bianca Müller & Andreas Deussen

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  1. Irakli Kopaliani
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Correspondence to Andreas Deussen.

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Kopaliani, I., Martin, M., Zatschler, B. et al. Cell-specific and endothelium-dependent regulations of matrix metalloproteinase-2 in rat aorta. Basic Res Cardiol 109, 419 (2014). https://doi.org/10.1007/s00395-014-0419-8

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  • DOI: https://doi.org/10.1007/s00395-014-0419-8

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