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Cardiopulmonary bypass induces the synthesis and release of matrix metalloproteinases
C Joffs1, H R Gunasinghe, M M Multani
1Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston 29425, USA.
Background:
A number of cellular and molecular events can be induced after cardiac procedures requiring cardiopulmonary bypass (CPB). The matrix metalloproteinases (MMPs) are a recently discovered family of enzymes that degrade the extracellular matrix, but expression during and after CPB is unknown.
Methods:
Systemic plasma MMP levels were measured in patients (n = 28, 63 +/- 1 years) undergoing elective coronary revascularization requiring CPB at baseline, termination of CPB, and 30 minutes, 6 and 24 hours after CPB. Representative classes of MMP species known to degrade matrix and basement membrane components were selected for study. Specifically, the interstitial collagenases MMP-8 and MMP-13, and the gelatinases MMP-2 and MMP-9 were determined by internally validated enzyme-linked immunosorbent assay.
Results:
The MMP-8 levels increased by fourfold at separation from CPB, and returned to within normal values within 30 minutes after CPB. The proenzyme forms of MMP-13 and MMP-9 increased by more than twofold at cross-clamp release and returned within normal limits within 6 hours after CPB. The proform of MMP-2 increased from baseline values at 6 and 24 hours postoperatively; likely indicative of de novo synthesis.
Conclusions:
A specific portfolio of MMPs are released and synthesized during and after CPB. Because MMPs can degrade extracellular proteins essential for maintaining normal cellular architecture and function, enhanced MMP release and activation may contribute to alterations in tissue homeostasis in the early postoperative period.
Insights
Matrix metalloproteinases (MMPs) are released during and after cardiopulmonary bypass (CPB). Elevated MMP levels post-surgery may affect tissue homeostasis.
Area of Science:
- Cardiovascular Surgery
- Biochemistry
- Enzymology
Background:
- Cardiopulmonary bypass (CPB) can induce cellular and molecular changes.
- Matrix metalloproteinases (MMPs) degrade extracellular matrix, but their expression during CPB is unknown.
Purpose of the Study:
- To investigate the expression of matrix metalloproteinases (MMPs) during and after cardiac procedures requiring cardiopulmonary bypass (CPB).
Main Methods:
- Systemic plasma MMP levels (MMP-8, MMP-13, MMP-2, MMP-9) were measured in 28 patients undergoing coronary revascularization requiring CPB.
- Measurements were taken at baseline, CPB termination, and 30 minutes, 6, and 24 hours post-CPB using enzyme-linked immunosorbent assays.
Main Results:
- MMP-8 levels increased fourfold at CPB separation, returning to normal within 30 minutes.
- MMP-13 and MMP-9 increased over twofold at cross-clamp release, normalizing within 6 hours.
- MMP-2 levels increased at 6 and 24 hours postoperatively, suggesting de novo synthesis.
Conclusions:
- A specific set of MMPs are released and synthesized during and after CPB.
- Enhanced MMP release and activation may contribute to early postoperative tissue homeostasis alterations due to extracellular protein degradation.