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Metalloproteinases 2 and 9 are increased in plasma of patients with heart failure
P Altieri1, C Brunelli, S Garibaldi
1Department of Internal Medicine, University of Genova, Genova, Italy.
Insights
Elevated plasma levels of matrix metalloproteinase-9 and matrix metalloproteinase-2 activity were found in heart failure patients, indicating ongoing extracellular remodeling. These findings suggest potential new biomarkers for heart failure progression.
Area of Science:
- Cardiovascular Research
- Biochemistry
- Molecular Biology
Background:
- Heart failure progression is linked to interstitial changes within the heart and in distant tissues.
- Previous studies noted enhanced matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in ventricular tissue of heart failure patients.
- This study investigated MMP-2, MMP-9, TIMP-1, and TIMP-2 activity in the plasma of heart failure patients.
Purpose of the Study:
- To determine if plasma activity levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 are elevated in patients with heart failure.
- To explore potential correlations between these protein levels and clinical parameters in heart failure.
Main Methods:
- Plasma samples were collected from 51 heart failure patients and 52 healthy controls.
- Gelatinolytic activity (zymography) and protein levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured.
- Statistical comparisons were made between patient and control groups.
Main Results:
- Heart failure patients showed significantly increased plasma activity of proMMP-9, active MMP-9, and proMMP-2 compared to controls.
- TIMP-1 protein levels were higher in patients, but TIMP-2 levels did not differ significantly.
- MMP levels correlated with clinical parameters like left ventricular volumes, white blood cell counts, and liver enzymes, but not NYHA class.
Conclusions:
- Elevated plasma activity and protein levels of MMPs suggest persistent extracellular remodeling in heart failure patients.
- These findings highlight the potential of circulating MMPs as biomarkers for heart failure.
- The study indicates that extracellular matrix remodeling is a continuous process in heart failure, irrespective of clinical stage.
Background:
Progression of heart failure is associated with interstitial changes in the heart and in areas distant from the heart. Enhanced expression of metalloproteinases 2 and 9 and of metalloproteinases tissue inhibitors 1 and 2 have been found in ventricular tissue of patients with heart failure. Our aim was to determine whether increased activity of metalloproteinase-2, metalloproteinase-9 and of metalloproteinases tissue inhibitor-1 and metalloproteinases tissue inhibitor-2 were also present in plasma of patients with heart failure.
Design:
Levels of metalloproteinase-2, metalloproteinase-9 and of metalloproteinase tissue inhibitor-1 and metalloproteinases tissue inhibitor-2 were measured in venous blood of 51 patients with heart failure, and were compared with levels of 52 control subjects. Samples collected from patients and control subjects were assayed for gelatinolytic activity (zymography) and for protein levels.
Results:
Compared with the control subjects, the patients with heart failure had a significant increase in activity levels (mean +/- SE, ng mL(-1)) of prometalloproteinase-9 (95.1+/-11.2 and 38.9+/-4.5*), activ. metalloproteinase-9 (18.4+/-2.5 and 10.9+/-1.3*), and of prometalloproteinase-2 (571.4+/-26.1 and 456.8+/-21.1*) (respectively: patients and control subjects; *P<0.05). Metalloproteinases tissue inhibitor-1, but not metalloproteinases tissue inhibitor-2 protein values were higher in the patients. Among the patients, clinical status and New York Heart Association (NYHA) class did not correlate with the metalloproteinase concentrations. Positive correlations with left ventricular volumes, and negative correlations with lipid values were obtained for prometalloproteinase-2; positive correlations with total number of white cells and neutrophils were obtained for prometalloproteinase-9; and positive correlations with lactate dehydrogenase, serum fibrinogen, aspartate transaminases were found for activ. metalloproteinase-9.
Conclusions:
Regardless of the clinical phase of heart failure, elevated levels of activity and of circulating metalloproteinase protein levels suggest the presence of persistent extracellular remodeling in patients with heart failure.
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