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Tarin, Carlos Lavín Plaza, Begoña Gomez, Monica Saura, Marta Diez-Juan, Antonio Zaragoza, Carlos 2024-01-30T13:31:58Z 2024-01-30T13:31:58Z 2011 Tarin, Carlos, et al. «The Extracellular Matrix Metalloproteinase Inducer EMMPRIN Is a Target of Nitric Oxide in Myocardial Ischemia/Reperfusion». Free Radical Biology and Medicine, vol. 51, n.o 2, julio de 2011, pp. 387-95. https://doi.org/10.1016/j.freeradbiomed.2011.04.021. 0891-5849 10.1016/j.freeradbiomed.2011.04.021 https://hdl.handle.net/20.500.14352/96575 https://doi.org/10.1016/j.freeradbiomed.2011.04.021 Nitric oxide (NO) is an important defense against myocardial ischemia/reperfusion (I/R) injury. Although matrix metalloproteinase (MMP)-mediated necrosis of cardiac myocytes is well characterized, the role of inducible NO synthase (iNOS)-derived NO in this process is poorly understood. I/R injury was increased in iNOS-deficient mice and in mice treated with 1400 W (a pharmacological iNOS inhibitor) and was associated with significantly increased expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and EMMPRIN-associated MMPs. Transcriptional activity of an EMMPRIN luciferase promoter reporter expressed in cardiac myocytes was inhibited by NO in a cGMP-dependent manner, and this transcriptional inhibition was abolished by mutation of a putative E2F site. Consistent with these findings, EMMPRIN null mice, in which iNOS is normally induced, are partially protected against I/R injury. Pharmacological inhibition of iNOS in EMMPRIN null mice had no additional protective effect, suggesting that EMMPRIN is a downstream target of NO. Administration of anti-EMMPRIN neutralizing antibodies partly reduced the excess heart damage and MMP-9 expression induced by I/R in iNOS null mice, indicating that regulation of EMMPRIN is an important mechanism of NO-mediated cardioprotection. eng restricted access The extracellular matrix metalloproteinase inducer EMMPRIN is a target of nitric oxide in myocardial ischemia/reperfusion journal article