Mechanisms of endothelial cell damage in systemic sclerosis and Raynaud's phenomenon.
OBJECTIVE
To investigate tumor necrosis factor (TNF), circulating immune complexes (CIC) and oxidized lipoproteins [measured as thiobarbituric acid reactive substances (TBARS)] as mediators of damage to endothelial cells (EC) in systemic sclerosis (SSc) and Raynaud's phenomenon (RP).


METHODS
In addition to CIC, TBARS and TNF, von Willebrand factor (vWF), angiotensin converting enzyme (ACE) and EC cytotoxicity were measured as markers of EC damage. C-reactive protein (CRP) and rheumatoid factor (RF) were measured as indicators of inflammation.


RESULTS
There were increases in TBARS and CIC, vWF and EC cytotoxicity, and CRP, with reduced levels of ACE. There were no correlations between any possible mediator of damage (TNF, TBARS, CIC) and indicators of such injury to the endothelium (vWF, ACE, EC cytotoxicity) except an inverse correlation between vWF and ACE. When patients with SSc were classified into those with limited disease (ISSc) or diffuse disease (dSSc), only wWF was different, being higher in patients with dSSc. In RP, vWF, RF and TBARS were again raised and ACE was lower. The only correlation was inversely between vWF and ACE.


CONCLUSIONS
Our results are suggestive of injury to the endothelium in both SSc and RP, with greater damage in patients with dSSc. Although there were multiple abnormalities in biochemical and immunological indices, there were no consistent correlations to explain the clear damage to the vasculature. We conclude that additional mechanisms other than TNF, CIC and lipid peroxides may be responsible for the insult to the vascular tree so evident in these patients.
Blann
A D
AD
University Department of Surgery, University Hospital of South Manchester, UK.
Illingworth
K
K
Jayson
M I
MI
D000328:Adult; D000368:Aged; D000936:Antigen-Antibody Complex / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011928:Raynaud Disease / Q000473:pathology / Q000503:physiopathology*; D012595:Scleroderma, Systemic / Q000473:pathology / Q000503:physiopathology*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014841:von Willebrand Factor / Q000032:analysis
D000936:Antigen-Antibody Complex; D017392:Thiobarbituric Acid Reactive Substances; D014841:von Willebrand Factor; D002097:C-Reactive Protein; D007703:Peptidyl-Dipeptidase A