Spatial differences of matrix metalloproteinase-2 and matrix metalloproteinase-9 within abdominal aortic aneurysm wall and intraluminal thrombus

J Physiol Pharmacol. 2016 Dec;67(6):903-910.

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.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aorta, Abdominal / metabolism*
  • Aortic Aneurysm, Abdominal / metabolism*
  • Female
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Middle Aged
  • Thrombosis / metabolism*
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism

Substances

  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9