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Thromb Haemost 2014; 111(02): 333-344
DOI: 10.1160/TH13-04-0309
Cellular Proteolysis and Oncology
Schattauer GmbH

Increased levels of lysosomal cysteinyl cathepsins in human varicose veins: A histology study

Na Xu
1   Department of Biological Sciences, School of Biotechnology & Food Engineering, Hefei University of Technology, Hefei, China
2   School of Life Science, University of Anhui Science & Technology, Fengyang, China
,
Yuan-Yuan Zhang
3   Department of Human Anatomy, Anhui Medical University, Hefei, China
,
Yan Lin
1   Department of Biological Sciences, School of Biotechnology & Food Engineering, Hefei University of Technology, Hefei, China
,
Bin Bao
1   Department of Biological Sciences, School of Biotechnology & Food Engineering, Hefei University of Technology, Hefei, China
,
Lei Zheng
1   Department of Biological Sciences, School of Biotechnology & Food Engineering, Hefei University of Technology, Hefei, China
,
Guo-Ping Shi
1   Department of Biological Sciences, School of Biotechnology & Food Engineering, Hefei University of Technology, Hefei, China
4   Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
,
Jian Liu
1   Department of Biological Sciences, School of Biotechnology & Food Engineering, Hefei University of Technology, Hefei, China
› Author Affiliations Financial support:This work was supported by the National Natural Science Foundation of China (Grant No. 31171315, to J.L.); by the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20100111110009, to J.L.); by the Anhui Provincial Natural Science Foundation of China (Grant No.11040606M92, to J.L.); by the Fundamental Research Funds for the Central Universities, China (Grant No.2012HGCX0003, to L.Z. and J.L.); and by the U.S. National Institutes of Health (Grant nos.HL60942, HL81090, and HL88547, to G.-P.S.).
Further Information

Publication History

Received: 16 April 2013

Accepted after major revision: 27 September 2013

Publication Date:
27 November 2017 (online)

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Summary

Varicose veins are a major chronic venous disease characterised by extensive remodelling of the extracellular matrix architecture in the vascular wall. Although matrix metalloproteinases have been implicated in these pathologic events, little is known about the functional relevance of other protease family members. Here, we studied the distribution of lysosomal cysteine proteases, cathepsins B, L, K, and S, and their endogenous inhibitor, cystatin C, in long saphenous vein specimens from nine normal donors and 18 patients with varicose veins (VVs). Immunohistochemical analysis demonstrated increased levels of cathepsins L, K, B, and S and reduced levels of cystatin C in VVs. This imbalance between cysteinyl cathepsins and cystatin C may favour VV remodelling. To investigate the inflammatory mechanism of their expression, we examined a detailed inflammatory cell profile in VVs, including macrophages, T lymphocytes, and mast cells. Increased numbers of CD3-positive T cells and tryptase-positive mast cells were found in VVs, and enhanced levels of cysteinyl cathepsins were detected from lesion CD3-positive T cells, chymase-positive mast cells, endothelial cells, and smooth-muscle cells. Elevated cathepsins, and their co-localisation to infiltrated inflammatory cells and to vascular cells, suggest that these proteases participate in extracellular matrix degradation in response to inflammation during VV pathogenesis.

Keywords

Cysteinyl cathepsin - cystatin C - varicose vein - inflammatory cell - vascular cell

 

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