Immune Cell and Vascular Dysfunction is Responsible for The connective Tissue Fibrosis in Scleroderma
Posted Sep 11 2009 4:58pm
Scleroderma is heterogeneous and life threatening and is characterised by the excessive extracellular matrix deposition within connective tissue of the body (i.e. skin and visceral organs). In addition to fibrosis, scleroderma is also characterised by prominent vascular and immunological abnormalities, that are associated with and often precede the fibrotic process.
It is therefore likely that immune cell and vascular dysfunction in this disease have a significant impact on the activation of the genetic programme that is responsible for the connective tissue fibrosis. Accumulated evidence over a number of years by many workers suggests that at least four distinct yet interactive components are involved in the initiation and progression of the disease process: (1) Vascular dysfunction in terms of alteration in vascular tone, endothelial cell activation/damage and oxidative stress; (2) an autoimmune process resulting in immune activation; (3) extravascular inflammation mediated by leukocytes; and (4) an uncontrolled connective tissue fibrosis.
Many studies have conducted investigations looking at single 'snapshots' in the evolution of the disease and measurable differences can be detected between patients and controls in a variety of parameters some of which include factors indicating a disturbance of leukocyte activity, and of endothelial cell function and fibroblast function.
However the inter-relationship between these parameters over disease evolution or organ based pathology is not well understood. Our current research efforts are therefore aimed at using complementary cell culture and molecular approaches to increase our knowledge of the pathogenesis of scleroderma. Read More.......