title: Extracellular matrix remodelling in response to venous hypertension: proteomics of human varicose veins.
abstract: Extracellular matrix remodelling has been implicated in a number of vascular conditions, including venous hypertension and varicose veins. However, to date, no systematic analysis of matrix remodelling in human veins has been performed.
  
  
  
  To understand the consequences of venous hypertension, normal and varicose veins were evaluated using proteomics approaches targeting the extracellular matrix. Varicose saphenous veins removed during phlebectomy and normal saphenous veins obtained during coronary artery bypass surgery were collected for proteomics analysis. Extracellular matrix proteins were enriched from venous tissues. The proteomics analysis revealed the presence of >150 extracellular matrix proteins, of which 48 had not been previously detected in venous tissue. Extracellular matrix remodelling in varicose veins was characterized by a loss of aggrecan and several small leucine-rich proteoglycans and a compensatory increase in collagen I and laminins. Gene expression analysis of the same tissues suggested that the remodelling process associated with venous hypertension predominantly occurs at the protein rather than the transcript level. The loss of aggrecan in varicose veins was paralleled by a reduced expression of aggrecanases. Chymase and tryptase β1 were among the up-regulated proteases. The effect of these serine proteases on the venous extracellular matrix was further explored by incubating normal saphenous veins with recombinant enzymes. Proteomics analysis revealed extensive extracellular matrix degradation after digestion with tryptase β1. In comparison, chymase was less potent and degraded predominantly basement membrane-associated proteins.
  
  
  
  The present proteomics study provides unprecedented insights into the expression and degradation of structural and regulatory components of the vascular extracellular matrix in varicosis.
authors.affiliation: King's British Heart Foundation Centre, King's College London, 125 Coldharbour Lane, London SE5 9NU, UK.
authors.forename: Javier
authors.initials: J
authors.lastname: Barallobre-Barreiro
authors.affiliation: Division of Vascular and Interventional Radiology, Mayo Clinic, Scottsdale, AZ, USA.
authors.forename: Rahmi
authors.initials: R
authors.lastname: Oklu
authors.affiliation: King's British Heart Foundation Centre, King's College London, 125 Coldharbour Lane, London SE5 9NU, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Lynch
authors.affiliation: King's British Heart Foundation Centre, King's College London, 125 Coldharbour Lane, London SE5 9NU, UK St George's Hospital, NHS Trust, London, UK.
authors.forename: Marika
authors.initials: M
authors.lastname: Fava
authors.affiliation: King's British Heart Foundation Centre, King's College London, 125 Coldharbour Lane, London SE5 9NU, UK.
authors.forename: Ferheen
authors.initials: F
authors.lastname: Baig
authors.affiliation: King's British Heart Foundation Centre, King's College London, 125 Coldharbour Lane, London SE5 9NU, UK.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Yin
authors.affiliation: King's British Heart Foundation Centre, King's College London, 125 Coldharbour Lane, London SE5 9NU, UK.
authors.forename: Temo
authors.initials: T
authors.lastname: Barwari
authors.affiliation: King's British Heart Foundation Centre, King's College London, 125 Coldharbour Lane, London SE5 9NU, UK.
authors.forename: David N
authors.initials: DN
authors.lastname: Potier
authors.affiliation: Division of Vascular Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Hassan
authors.initials: H
authors.lastname: Albadawi
authors.affiliation: St George's Hospital, NHS Trust, London, UK.
authors.forename: Marjan
authors.initials: M
authors.lastname: Jahangiri
authors.affiliation: Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Porter
authors.affiliation: Division of Vascular Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Watkins
authors.affiliation: Division of Vascular and Interventional Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Misra
authors.affiliation: Division of Vascular Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Julianne
authors.initials: J
authors.lastname: Stoughton
authors.affiliation: King's British Heart Foundation Centre, King's College London, 125 Coldharbour Lane, London SE5 9NU, UK manuel.mayr@kcl.ac.uk.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mayr
mesh_terms: D016022:Case-Control Studies; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D059748:Proteolysis; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D012501:Saphenous Vein / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D053719:Tandem Mass Spectrometry; D014648:Varicose Veins / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D066253:Vascular Remodeling; D014690:Venous Pressure
chemical_list: D016326:Extracellular Matrix Proteins
keywords: Extracellular matrix; Protease; Smooth Muscle; Venous