title: Increased levels of lysosomal cysteinyl cathepsins in human varicose veins: a histology study.
abstract: 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.
authors.forename: Na
authors.initials: N
authors.lastname: Xu
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.forename: Bin
authors.initials: B
authors.lastname: Bao
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Shi
authors.affiliation: Jian Liu, PhD, School of Biotechnology and Food Engineering, Hefei University of Technology, 193 Tunxi Road, Hefei, Anhui 230009, P. R. Republic of China, Tel.: +86 551 62901349, Fax:+86 551 62901331, E-mail: liujian509@gmail.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D002403:Cathepsins / Q000032:analysis*; D055316:Cystatin C / Q000032:analysis; D042783:Endothelial Cells / Q000201:enzymology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000201:enzymology; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology; D012501:Saphenous Vein / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000201:enzymology; D015854:Up-Regulation; D014648:Varicose Veins / Q000201:enzymology* / Q000276:immunology / Q000473:pathology
chemical_list: D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D002403:Cathepsins
keywords: Cysteinyl cathepsin; cystatin C; inflammatory cell; varicose vein; vascular cell