RT info:eu-repo/semantics/article
T1 Nitric Oxide Induces Cardiac Protection by Preventing Extracellular Matrix Degradation through the Complex Caveolin-3/EMMPRIN in Cardiac Myocytes.
A1 Cuadrado Berrocal, Irene
A1 Castejón, Borja
A1 Martín, Ana María
A1 Saura Redondo, Marta
A1 Reventun Torralba, Paula
A1 Zamorano Gómez, José Luís
A1 Zaragoza Sánchez, Carlos
K1 Extracellular Matrix
K1 Myocardial Reperfusion Injury
K1 Myocytes, Cardiac
K1 Nitric Oxide
K1 Protective Agents
K1 Fisiología
K1 Physiology
K1 Animals
K1 Basigin
K1 Caveolin 3
K1 Cell Line
K1 Extracellular Matrix
K1 Glycosylation
K1 Hydrazines
K1 Immunoblotting
K1 Mice
K1 Mice, Knockout
K1 Microscopy, Confocal
K1 Multiprotein Complexes
K1 Myocardial Infarction
K1 Myocardial Reperfusion Injury
K1 Myocytes, Cardiac
K1 Nitric Oxide
K1 Nitric Oxide Donors
K1 Nitric Oxide Synthase Type II
K1 Protective Agents
AB Inhibition of Extracellular Matrix degradation by nitric oxide (NO) induces cardiac protection against coronary ischemia/reperfusion (IR). Glycosylation of Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) stimulates enzymatic activation of matrix metalloproteinases (MMPs) in the heart, although the mechanisms leading to EMMPRIN glycosylation are poorly understood. We sought to determine if NO may induce cardiac protection by preventing glycosylation of EMMPRIN in a mouse model of IR. Here we found that Caveolin-3 binds to low glycosylated EMMPRIN (LG-EMMPRIN) in cardiac cells and in the hearts of healthy mice, whereas IR disrupted the complex in nitric oxide synthase 2 (NOS2) knockout (KO) mice. By contrast, the binding was partially restored when mice were fed with an NO donor (DEA-NO) in the drinking water, showing a significant reduction on infarct size (NOS2KO: 34.6±5 vs NOS2KO+DEA-NO: 20.7±9), in expression of matrix metalloproteinases, and cardiac performance was improved (left ventricular ejection fraction (LVEF). NOS2KO: 31±4 vs NOS2KO+DEA-NO: 46±6). The role of Caveolin-3/EMMPRIN in NO-mediated cardiac protection was further assayed in Caveolin-3 KO mice, showing no significant improvement on infarct size (Caveolin-3 KO: 34.8±3 vs Caveolin-3 KO+DEA-NO:33.7±5), or in the expression of MMPs, suggesting that stabilization of the complex Caveolin-3/LG-EMMPRIN may play a significant role in the cardioprotective effect of NO against IR.
PB Utpal Sen, University of Louisville, UNITED STATES
YR 2016
FD 2016-09-20
LK http://hdl.handle.net/10017/33764
UL http://hdl.handle.net/10017/33764
LA eng
NO Ministerio de Economía y Competitividad
DS MINDS@UW
RD 26-abr-2024