PUMA
Istituto di Fisiologia Clinica     
Caruso R., Caselli C., Boroni C., Campolo J., Milazzo F., Cabiati M., Russo C., Parolini M., Giannessi D., Frigerio M., Parodi O. Relationship Between Myocardial Redox State and Matrix Metalloproteinase Activity in Patients on Left Ventricular Assist Device Support. In: Circulation Journal, vol. 75 pp. 2387  - 2396. Circulation Journal, 2011.
 
 
Abstract
(English)
Background:  Redox aminothiols have been reported to modulate the activity of recombinant metalloproteinases  (MMP). The aim of the present study was to investigate the effects of myocardial redox state on the activities of  MMP-2 and -9 implicated in cardiac remodeling in end-stage heart failure patients supported by left ventricular assist  device (LVAD). Methods and Results:  During heart transplant (HT) surgery, myocardial specimens (MS) from right ventricular  walls and LV walls were obtained from 7 LVAD recipients (LVAD group, MS n=35) and from 7 stable HT candidates  on medical therapy (MT group, MS n=35). Myocardial MMP-2 and -9 activities and expression, tissue inhibitor of  MMP (TIMP)-1 and -4, transforming growth factor (TGF)-β1 and aminothiol concentrations were measured. MMP-2  and -9 activities were evaluated also by incubating MS with different amounts of reduced and oxidized glutathione  (GSH). MMP-2 and -9 activities and expression were lower in the LVAD group, whereas myocardial TIMP-1 and -4  concentrations were comparable to those of MT patients. Higher GSH  and TGF-β1 concentrations were found   in LVAD-recipients. Only GSH concentrations were inversely related to MMP-2 and -9 activities. In vitro, GSH had  an inhibitory effect on MMP-2 and -9 activities. Conclusions:  LVAD recipients show reduced myocardial MMP-2 and -9 activities and expression when compared  to medically treated patients. Changes of myocardial redox state, predominantly GSH-dependent, appear to modu- late MMP-2 and -9 activities by an inhibitory effect dependent on thiol content. These data support a role of GSH  cycle in modulating the extracellular matrix in end-stage heart failure patients supported by LVAD.   
Subject Myocardial Redox State, MMPs, Left Ventricular Assist Device Support


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