Related Experiment Video
Updated: May 30, 2026
Reduction in Left Ventricular Wall Stress and Improvement in Function in Failing Hearts using Algisyl-LVR
Published on: April 8, 2013
Relationship between myocardial redox state and matrix metalloproteinase activity in patients on left ventricular
Raffaele Caruso1, Chiara Caselli, Chiara Boroni
1CNR Clinical Physiology Institute, Cardiovascular Department, Niguarda Cà Granda Hospital Milan, Milan, Italy.
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 modulate 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.
Insights
Reduced myocardial matrix metalloproteinase (MMP)-2 and -9 activity in left ventricular assist device (LVAD) patients is linked to redox state changes. Glutathione (GSH) inhibits MMP activity, suggesting a role in extracellular matrix modulation for heart failure.
Area of Science:
- Cardiology
- Biochemistry
- Biomedical Engineering
Background:
- Matrix metalloproteinases (MMPs), specifically MMP-2 and MMP-9, are implicated in cardiac remodeling.
- Redox aminothiols are known to modulate metalloproteinase activity.
- Understanding myocardial redox state effects on MMPs is crucial in end-stage heart failure.
Purpose of the Study:
- To investigate the impact of myocardial redox state on MMP-2 and MMP-9 activities in patients with end-stage heart failure supported by left ventricular assist device (LVAD).
- To compare MMP activities and related factors between LVAD recipients and medically treated heart failure patients.
Main Methods:
- Myocardial specimens were collected from LVAD recipients and medically treated heart failure patients during heart transplant surgery.
- Assays were performed to measure myocardial MMP-2 and -9 activities and expression, tissue inhibitors of MMP (TIMP)-1 and -4, transforming growth factor (TGF)-β1, and aminothiol concentrations.
- In vitro experiments assessed the effect of reduced and oxidized glutathione (GSH) on MMP-2 and -9 activities.
Main Results:
- LVAD recipients exhibited lower myocardial MMP-2 and -9 activities and expression compared to medically treated patients.
- Higher concentrations of glutathione (GSH) and transforming growth factor (TGF)-β1 were observed in LVAD recipients.
- Glutathione (GSH) concentrations were inversely correlated with MMP-2 and -9 activities, and GSH demonstrated an inhibitory effect in vitro.
Conclusions:
- Left ventricular assist device (LVAD) recipients show decreased myocardial MMP-2 and -9 activity and expression relative to medically treated patients.
- Myocardial redox state, particularly influenced by GSH, modulates MMP-2 and -9 activities through an inhibitory mechanism.
- The glutathione (GSH) cycle plays a significant role in modulating the extracellular matrix in LVAD-supported end-stage heart failure patients.
Related Concept Videos
01:14Myocarditis III: Medical Management
01:21Myocarditis I: Introduction