Vascular damage and lack of angiogenesis in systemic sclerosis skin.

The aim of this study was to analyse microvascular damage and compensatory angiogenesis in skin from patients with systemic sclerosis (SSc) compared with systemic lupus erythematosus (SLE), Raynaud's phenomenon (RP) and healthy controls. Immunohistochemistry was used for skin biopsies (9 SSc, 10 SLE, 9 RP and 12 healthy controls) using von Willebrand factor and beta3 integrin subunit specific antibodies, TechMate immunostaining robot and biotin-streptavidin protocol. In the early stages of SSc, vWF was found in the perivascular space and interstitial matrix in papillary but not in the reticular dermis, in particular around small oedematous blood vessels infiltrated by mononuclear cells. The extravascular release of vWF in SSc specimens was associated with weak or even a total lack of immunoreactivity within the associated endothelial cells. Late stages of SSc were characterised by loss of the dermal papillae, subepidermal fibrosis, hypovascularity and strong endothelial vWF expression without extravascular leakage. In all SSc patients studied only a few vascular profiles were weakly immunostained for beta3 integrin subunit. This work demonstrates that vWF is not only released into the systemic circulation, but is also leaked to the perivascular space/matrix. This local release and deposition of vWF is probably a sensitive and early marker of microvascular involvement in SSc pathogenesis. Local vWF release may play a role in platelet adhesion, aggregation, thrombogenesis and dermal connective tissue remodelling. In spite of some attempts towards compensatory angiogenesis in SSc, as evidenced by beta3 integrin subunit expression, it was evident that the angiogenic response was not able to prevent the development of hypovascularity during the advanced stages of the disease.