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Matrix metalloproteinase levels in chronic thoracic aortic dissection
Xiaoming Zhang1, Darrell Wu2, Justin C Choi3
1Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Department of Cardiovascular Surgery, Texas Heart Institute, Houston, Texas; Department of Pathophysiology, Shandong University School of Medicine, Jinan, Shandong, China.
Background:
Imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) can lead to aortic wall failure. We hypothesized that patients with aneurysms resulting from chronic descending thoracic aortic dissection have elevated tissue and plasma levels of specific MMPs and decreased tissue levels of TIMPs.
Materials And Methods:
Aortic tissue was obtained from 25 patients who required surgical repair of descending thoracic aortic aneurysm due to chronic aortic dissection and from 17 organ-donor controls without aortic disease. Tissue levels of MMP-1, -2, -3, -9, -12, and -13 and TIMP-1 and -2 were measured by colorimetric activity assay or enzyme-linked immunosorbent assay and confirmed by Western blot and immunohistochemistry. Blood obtained from the 25 patients and 15 controls without aortic diseases was used to compare plasma levels of MMP-3, -9, and -12.
Results:
Total MMP-1, total MMP-9, and active MMP-9 levels were higher and total MMP-2 levels were lower in dissection tissue than in control tissue. Additionally, the MMP-9 to TIMP-1 and active to total MMP-2 ratios were higher and the MMP-2 to TIMP-2 ratio was lower in dissection tissue. Furthermore, patients had higher plasma active to total MMP-9 ratios than the controls. Age and hypertension were associated with increased MMP levels.
Conclusions:
Increased levels of several MMPs and increased MMP to TIMP ratios in aortic tissue from patients suggest an environment that favors proteolysis, which may promote progressive extracellular matrix destruction and medial degeneration after aortic dissection. An elevated active to total MMP-9 ratio in plasma may be a biomarker for end-stage aneurysm development in patients with chronic thoracic aortic disease.
Insights
Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) imbalance contributes to aortic wall failure. This study found higher MMP levels and MMP to TIMP ratios in dissection tissue, suggesting proteolysis promotes aortic degeneration. An elevated MMP-9 ratio in plasma may indicate end-stage aneurysm development.
Area of Science:
- Cardiovascular Biology
- Proteomics
- Aortic Disease Research
Background:
- Imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) is implicated in aortic wall failure.
- Chronic descending thoracic aortic dissection can lead to aneurysms due to extracellular matrix degradation.
Purpose of the Study:
- To investigate tissue and plasma levels of specific MMPs and TIMPs in patients with aneurysms from chronic descending thoracic aortic dissection.
- To determine if MMP and TIMP levels correlate with aortic dissection and aneurysm development.
Main Methods:
- Aortic tissue and plasma samples were collected from patients with descending thoracic aortic aneurysms and organ-donor controls.
- Levels of MMP-1, -2, -3, -9, -12, -13 and TIMP-1, -2 were measured using various assays and confirmed by Western blot and immunohistochemistry.
- Plasma levels of MMP-3, -9, and -12 were compared between patients and controls.
Main Results:
- Dissection tissue showed higher total MMP-1, total MMP-9, and active MMP-9, with lower total MMP-2 compared to controls.
- Elevated MMP-9 to TIMP-1 and active to total MMP-2 ratios, and a lower MMP-2 to TIMP-2 ratio were observed in dissection tissue.
- Patients exhibited higher plasma active to total MMP-9 ratios; age and hypertension correlated with increased MMP levels.
Conclusions:
- Elevated MMPs and MMP to TIMP ratios in aortic tissue suggest a pro-proteolytic environment contributing to extracellular matrix destruction and medial degeneration post-dissection.
- An increased active to total MMP-9 ratio in plasma may serve as a biomarker for end-stage aneurysm development in chronic thoracic aortic disease.
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