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Published on: August 24, 2019
Spatial differences of matrix metalloproteinase-2 and matrix metalloproteinase-9 within abdominal aortic aneurysm
A Siennicka1, M Zuchowski2, M Kaczmarczyk3
1Department of Laboratory Diagnostics, Pomeranian Medical University, Szczecin, Poland. asienn@pum.edu.pl.
Abstract:
Formation of an abdominal aortic aneurysm is a complex process involving aortic wall degradation. The matrix metalloproteinases (MMPs) mainly involved in this process are MMP-2 and MMP-9. Most aneurysms contain an intraluminal thrombus. It is suggested that the thrombus' thickness correlates with the risk of aneurysm rupture and may be a new prognostic factor. The purpose of the present study was to investigate enzyme protein levels in thick (A1) and thin (B1) segments of the thrombus and aneurysm wall sections A (adjacent to A1) and B (adjacent to B1). Aneurysm samples from one aneurism sac were collected from 36 patients that underwent aneurysm repair. MMP-2, MMP-9 and a tissue inhibitor of metalloproteinases (TIMP-1) were measured using enzyme-linked-immunosorbent assay of protein extract. MMP-9 concentrations were significantly higher in B1 samples compared with A1 (113.4 ± 118.0 versus 63.0 ± 61.2, P = 0.004), A(113.4 ± 118.0 versus 31.7 ± 30.0, P < 0.001) or B (113.4 ± 118.0 versus 39.5 ± 41.5, P < 0.001). Likewise MMP-9/TIMP-1 ratio was elevated in B1 compared with A1 (18.9 ± 27.8 versus 9.1 ± 10.6, P = 0.017), A (18.9 ± 27.8 versus 2.5 ± 2.2, P < 0.001) or B (18.9 ± 27.8 versus 3.6 ± 4.5, P < 0.001). MMP-2 and TIMP-1 were higher in A compared with A1 (18.4 ± 8.5 versus 7.2 ± 7.6, P < 0.001; 14.3 ± 5.9 versus 8.5 ± 5.4, P < 0.001, respectively) and B1 (18.4 ± 8.5 versus 5.2 ± 2.9, P < 0.001; 14.3 ± 5.9 versus 8.9 ± 4.9, P < 0.001, respectively) as well as in B compared with A1 (15.9 ± 7.3 versus 7.2 ± 7.6, P < 0.001; 13.0 ± 5.0 versus 8.5 ± 5.4, P < 0.001, respectively) and B1 (15.9 ± 7.3 versus 5.2 ± 2.9, P < 0.001; 13.0 ± 5.0 versus 8.9 ± 4.9, P = 0.003, respectively). There were significant correlations between thin thrombus TIMP-1 and thrombus thickness (β = -0.24, P = 0.021) and between thin thrombus MMP-9/TIMP-1 ratio and thrombus thickness (β = 1.75, P = 0.003). Our study has revealed that the presence of thrombi with thin segments in the aneurysm sac, associated with higher proteolytic activity, could possibly be used as a potential indicator of a rupture site.
Insights
Thin thrombus segments in abdominal aortic aneurysms show higher matrix metalloproteinase-9 (MMP-9) activity. This increased proteolytic activity in thin thrombus areas may indicate a higher risk of aneurysm rupture.
Area of Science:
- Cardiovascular Biology
- Vascular Surgery
- Biochemistry
Background:
- Abdominal aortic aneurysm (AAA) formation involves aortic wall degradation mediated by matrix metalloproteinases (MMPs), primarily MMP-2 and MMP-9.
- Intraluminal thrombus is common in AAA, and its thickness may correlate with rupture risk.
Purpose of the Study:
- To investigate enzyme protein levels (MMP-2, MMP-9, TIMP-1) in thick and thin segments of AAA thrombus and adjacent aneurysm walls.
- To explore the relationship between thrombus thickness, proteolytic activity, and potential rupture risk.
Main Methods:
- Analysis of aneurysm samples from 36 patients undergoing AAA repair.
- Measurement of MMP-2, MMP-9, and TIMP-1 protein levels using enzyme-linked-immunosorbent assay (ELISA).
- Comparison of enzyme levels between thick thrombus (A1), thin thrombus (B1), and adjacent wall sections (A, B).
Main Results:
- MMP-9 concentrations and MMP-9/TIMP-1 ratios were significantly higher in thin thrombus segments (B1) compared to thick thrombus (A1) and adjacent wall sections (A, B).
- MMP-2 and TIMP-1 levels were higher in aneurysm wall sections (A, B) compared to both thick (A1) and thin (B1) thrombus segments.
- Significant correlations were found between thin thrombus TIMP-1, MMP-9/TIMP-1 ratio, and overall thrombus thickness.
Conclusions:
- Thin thrombus segments within AAA sacs exhibit elevated proteolytic activity, characterized by higher MMP-9 levels and MMP-9/TIMP-1 ratios.
- This heightened proteolytic activity in thinner thrombus areas suggests they may serve as potential indicators of AAA rupture sites.
- Thrombus characteristics, particularly thin segments, warrant further investigation as prognostic factors for AAA rupture risk.
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