Proteomic profiling of the human venous extracellular matrix reveals a role for mast cell proteases in the pathogenesis of varicose veins

Purpose Venous hypertension in the hepatic, splanchnic and peripheral circulation is associated with significant morbidity and mortality affecting a large population of patients comprised of liver, renal and pulmonary disease. To understand the pathogenesis of human venous hypertension, normal and varicose veins were evaluated using a novel proteomic discovery approach targeting only the extracellular matrix (ECM) proteins. Materials and Methods Varicose saphenous veins removed during phlebectomy and normal saphenous veins obtained during cardiac surgery were collected for proteomics analysis. Following our solubility-based subfractionation methodology (1), ECM proteins were sequentially isolated, deglycosylated, separated by SDS-PAGE and identified using liquid chromatography tandem mass spectrometry (LC-MS/MS). Each tissue sample was further evaluated by histology (toluidine blue, hematoxylin and eosin and Mason’s trichrome stains), immunohistochemistry and Western blot analysis. Results Our proteomic analysis of the human vein ECM revealed 84 proteins, of which 13 proteins demonstrated significant differences in their quantity between the two types of venous tissue (p Conclusion Our proteomics discovery approach suggests that mast cells play a pivotal role in the pathogenesis of venous hypertension. Mast cell proteases, specifically chymase, can degrade components of the ECM, induce inflammation and apoptosis of smooth muscle cells, and activate down-stream pathways that can lead to the development of varicosis. Reference 1. Didangelos A et al. Mol Cell Proteomics. 2011 10(8):M111