RT Journal Article
T1 The extracellular matrix metalloproteinase inducer EMMPRIN is a target of nitric oxide in myocardial ischemia/reperfusion
A1 Tarin, Carlos
A1 Lavín Plaza, Begoña
A1 Gomez, Monica
A1 Saura, Marta
A1 Diez-Juan, Antonio
A1 Zaragoza, Carlos
AB 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.
PB Elsevier
SN 0891-5849
YR 2011
FD 2011
LK https://hdl.handle.net/20.500.14352/96575
UL https://hdl.handle.net/20.500.14352/96575
LA eng
NO 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.
DS Docta Complutense
RD 6 abr 2025