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Cardiovasc Res. 2016 Jun 1;110(3):419-30. doi: 10.1093/cvr/cvw075. Epub 2016 Apr 11.

Extracellular matrix remodelling in response to venous hypertension: proteomics of human varicose veins.

Author information

1
King's British Heart Foundation Centre, King's College London, 125 Coldharbour Lane, London SE5 9NU, UK.
2
Division of Vascular and Interventional Radiology, Mayo Clinic, Scottsdale, AZ, USA.
3
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.
4
Division of Vascular Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
5
St George's Hospital, NHS Trust, London, UK.
6
Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
7
Division of Vascular and Interventional Radiology, Mayo Clinic, Rochester, MN, USA.
8
King's British Heart Foundation Centre, King's College London, 125 Coldharbour Lane, London SE5 9NU, UK manuel.mayr@kcl.ac.uk.

Abstract

AIMS:

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.

METHODS AND RESULTS:

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.

CONCLUSION:

The present proteomics study provides unprecedented insights into the expression and degradation of structural and regulatory components of the vascular extracellular matrix in varicosis.

KEYWORDS:

Extracellular matrix; Protease; Smooth Muscle; Venous

PMID:
27068509
PMCID:
PMC4872879
DOI:
10.1093/cvr/cvw075
[Indexed for MEDLINE]
Free PMC Article

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