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TIMP 的抑制作用影响静脉曲张的形态。

Inhibitory effect of TIMP influences the morphology of varicose veins.

机构信息

Department of Surgery and Cancer, Faculty of Medicine, Imperial College, and Department of Histopathology, Charing Cross Hospital, London, UK.

出版信息

Eur J Vasc Endovasc Surg. 2010 Dec;40(6):754-65. doi: 10.1016/j.ejvs.2010.04.028. Epub 2010 Jul 3.

Abstract

OBJECTIVES

Imbalance of matrix metalloproteinase enzymes (MMP) and their inhibitors (TIMPs) may contribute to the development of varicose veins. We hypothesised that, histological changes in varicose vein wall correlate with alterations in expression of MMP/TIMP.

METHODS

Varicose veins (n=26) were compared with great saphenous vein (GSV) segments (n=11) from arterial bypass, and with arm and neck veins from fistula and carotid operations (n=13). Varicose vein wall thickness was measured, enabling categorisation as atrophic and hypertrophic. MMP-2, MT1-MMP, TIMP-2, and TIMP-3 expression were quantitatively analysed by immunohistochemistry.

RESULTS

There was significantly higher expression of TIMP-2 (immunopositive area 4.34% versus 0.26%), linked with connective tissue accumulation in the tunica media of varicose veins as compared with arm and neck vein controls. TIMP-2 and TIMP-3 expression was higher in hypertrophic than atrophic segments (3.2% versus 0.99% for TIMP-2, 1.7% versus 0.08% for TIMP-3). Similarly, TIMP-2 and TIMP-3 had elevated expression in the thicker proximal varicose vein segments compared to distal (4.3% versus 1.3% for TIMP-2 and 0.94% versus 0.41% for TIMP-3).

CONCLUSIONS

This study linked morphological changes in varicose vein walls with MMP/TIMP balance. A higher TIMP expression favours deposition of connective tissue and thus thicker vein wall, reducing matrix turnover by suppression of protease activity.

摘要

目的

基质金属蛋白酶(MMP)及其抑制剂(TIMP)的失衡可能导致静脉曲张的发生。我们假设静脉曲张壁的组织学变化与 MMP/TIMP 表达的改变有关。

方法

将静脉曲张(n=26)与动脉旁路的大隐静脉(GSV)段(n=11)以及瘘管和颈动脉手术的手臂和颈部静脉(n=13)进行比较。测量静脉曲张壁的厚度,以便将其分类为萎缩型和肥厚型。通过免疫组织化学定量分析 MMP-2、MT1-MMP、TIMP-2 和 TIMP-3 的表达。

结果

与手臂和颈部静脉对照组相比,TIMP-2 的表达(免疫阳性面积 4.34%对 0.26%)显著更高,与中膜结缔组织堆积有关。与萎缩段相比,肥厚段的 TIMP-2(3.2%对 0.99%)和 TIMP-3(1.7%对 0.08%)表达更高。同样,与远端相比,近端静脉曲张较厚的部位 TIMP-2(4.3%对 1.3%)和 TIMP-3(0.94%对 0.41%)表达更高。

结论

本研究将静脉曲张壁的形态变化与 MMP/TIMP 平衡联系起来。较高的 TIMP 表达有利于结缔组织的沉积,从而使静脉壁变厚,通过抑制蛋白酶活性减少基质的转化。

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