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Huh, Choi, and Kim: The Expression of Matrix Metalloproteinase according to Hydrostatic Pressure in Varicose Veins
Original Article
Journal of the Korean Surgical Society

Journal of the Korean Surgical Society 2009; 77(5): 344-352.

Published online: 6 November 2009

DOI: https://doi.org/10.4174/jkss.2009.77.5.344

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

Seung Huh, M.D., Hyang Hee Choi, M.D., Hyung-kee Kim, M.D.

Division of Transplantation and Vascular Surgery, Department of Surgery, Kyungpook National University School of Medicine, Daegu, Korea.

Corresponding author (shuh@knu.ac.kr)

Received 15 July 2009       Accepted 24 August 2009

Copyright © 2009 The Korean Surgical Society

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.

Keywords: Varicose veins, Hydrostatic pressure, Matrix metalloproteinases

Figures and Tables

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).
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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.
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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).
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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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Table 1
Mean degree of degeneration of varicose veins according to the wall and anatomical sites
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*n=9 in Dodd, n=10 in Boyd; †n=8 in Dodd and Boyd.

Table 2
Mean expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in control group
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*EC = endothelial cell; †Vasa = vasa vasorum; ‡MMP-9>TIMP-2>MMP-1=MMP-2=MMP-13>TIMP-1 (P<0.05).

Table 3
Mean expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in stress group
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*EC = endothelial cell; †Vasa =vasa vasorum; ‡MMP-9>TIMP-2>MMP-1>MMP-13>MMP-2>TIMP-1 (P<0.05).

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