Inhibition of MMP2 activity mitigates<i> N</i>-omega-nitro-l-arginine-methyl ester (L-NAME)-induced right heart failure - Research portal of Justus Liebig University Giessen:

Journal article

Inhibition of MMP2 activity mitigates N-omega-nitro-l-arginine-methyl ester (L-NAME)-induced right heart failure

Authors list: Schreckenberg, Rolf; Schulz, Rainer; Itani, Nadja; Ferdinandy, Peter; Bencsik, Peter; Szabados, Tamara; Rohrbach, Susanne; Niemann, Bernd; Schlueter, Klaus-Dieter

Publication year: 2024

Journal: Redox Biology

Volume number: 76

ISSN: 2213-2317

Open access status: Gold

DOI Link: https://doi.org/10.1016/j.redox.2024.103308

Publisher: Elsevier

Abstract:
In rats decreased bioavailability of nitric oxide induces oxidative stress and right heart failure. Oxidative stress can activate matrix metalloproteinase-2 (MMP2). We addressed the question whether increasing oxidative defense by administration of the SOD mimetic Tempol or direct inhibition of MMP2 activity by SB-3CT mitigates right heart failure. Rats received L-NAME for four weeks and during week three and four treatment groups received either Tempol or SB-3CT in addition. After four weeks heart function was analyzed by echocardiography, organ weights and expression of NPPB and COL1A1 were analyzed, oxidative stress was monitored by DHE-staining and MMP2 activity was quantified by proteolytic auto-activation, zymography, and troponin I degradation. L-NAME induced oxidative stress and MMP2 activity stronger in the right ventricle than in the left ventricle. Troponin I, a MMP2 substrate, was degraded in right ventricles. Tempol reduced oxidative stress and preferentially affected the expression of fibrotic genes (i.e. COL1A1) ) and fibrosis. Tempol and SB-3CT mitigated right but not left ventricular hypertrophy. Neither SB-3CT nor Tempol alone strongly improved right ventricular function. In conclusion, both MMP2 activity and oxidative stress contribute to right ventricular failure but neither is MMP2 activation linked to oxidative stress nor does oxidative stress and MMP2 activity have common targets.

Citation Styles

Harvard Citation style: Schreckenberg, R., Schulz, R., Itani, N., Ferdinandy, P., Bencsik, P., Szabados, T., et al. (2024) Inhibition of MMP2 activity mitigates N-omega-nitro-l-arginine-methyl ester (L-NAME)-induced right heart failure, Redox Biology, 76, Article 103308. https://doi.org/10.1016/j.redox.2024.103308

APA Citation style: Schreckenberg, R., Schulz, R., Itani, N., Ferdinandy, P., Bencsik, P., Szabados, T., Rohrbach, S., Niemann, B., & Schlueter, K. (2024). Inhibition of MMP2 activity mitigates N-omega-nitro-l-arginine-methyl ester (L-NAME)-induced right heart failure. Redox Biology. 76, Article 103308. https://doi.org/10.1016/j.redox.2024.103308

Keywords

Cardiac fibrosis; Myocardial hypertrophy