J Korean Surg Soc.  2009 Nov;77(5):344-352. 10.4174/jkss.2009.77.5.344.

The Expression of Matrix Metalloproteinase according to Hydrostatic Pressure in Varicose Veins

Affiliations
  • 1Division of Transplantation and Vascular Surgery, Department of Surgery, Kyungpook National University School of Medicine, Daegu, Korea. shuh@knu.ac.kr

Abstract

PURPOSE
The expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) caused by hydrostatic pressure stress is important in the development of varicose veins (VVs). This study was performed to analyse the expression of various MMPs and TIMPs according to the hydrostatic stress and the anatomical level of human great saphenous vein (GSV).
METHODS
Forty-nine vein samples were obtained from 10 patients with VVs (control group), and 34 samples from 7 VV patients after 1-hour hydrostatic stress just before surgery (stress group) at each anatomical site (proximal, Hunter, Dodd, and Boyd perforators) of GSV. Light microscopic examination and immunohistochemistry for MMP-1, -2, -9, -13 and TIMP-1, -2 were performed.
RESULTS
Intimal hyperplasia, fragmentation and loss of elastic fibers, infiltration of collagen fibers, and disorganization of medial muscle layers were evident in most vein samples. The degree of vein wall degeneration was not different between the 2 groups, and the anatomical sites of GSV. By immunohistochemistry, the expression of MMPs and TIMPs was not significantly different according to the group and the site. The expression of MMP-9 was more intense than that of other MMPs and TIMPs in all samples. MMP-9 was well localized to endothelial cells, medial muscle layers, and adventitial vasa vasorum.
CONCLUSION
There are no distinct differences in the varicose vein samples after short-term postural blood stasis compared to the resting group. MMP-9 may be the key enzyme of the venous wall remodeling.

Keyword

Varicose veins; Hydrostatic pressure; Matrix metalloproteinases

MeSH Terms

Collagen
Elastic Tissue
Endothelial Cells
Humans
Hydrostatic Pressure
Hyperplasia
Immunohistochemistry
Light
Matrix Metalloproteinases
Muscles
Saphenous Vein
Tissue Inhibitor of Metalloproteinase-1
Varicose Veins
Vasa Vasorum
Veins
Collagen
Matrix Metalloproteinases
Tissue Inhibitor of Metalloproteinase-1

Figure

  • Fig. 1 Histochemical staining of section of varicose vein shows changes of intimal and medial connective tissue elements. Diffuse intimal hyperplasia and disorganization of medial smooth muscle layers are seen (A) (Masson's trichrome; ×100). Black-stained elastic fibers are fragmented and lost in internal elastic lamina (black arrow) and medial smooth muscle layers (B) (Verhoff's elatic fiber; ×100).

  • Fig. 2 By histologic analysis, degenerative changes of the vein walls are more severe in both of intimal and medial layers of Dodd and Boyd sites in control groups (A), whereas in the intimal layers of proximal and Boyd sites in stress groups (B). I = intima; M = media.

  • Fig. 3 Immunohistochemical staining of varicose vein for matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) (×100). Focal brown-stained endothelial cells (black arrow) expressing MMP-1 (A), and tiny stained vasa vasorum (black arrow) expressing MMP-2 (B) in the sections of varicose vein. The MMP-9 expression is more diffuse and intense in the whole vein wall (C), and that of TIMP-2 is less than MMP-9 (D).

  • Fig. 4 By immunohistochemical analysis, the MMP-9 expression is more intense at medial layer compared to intima in both control and stress groups. I = intima; M = media.


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