Autoimmunity and vascular involvement in systemic sclerosis (SSc)

Endothelial injury, obliterative microvascular lesions, and increased vascu lar wall thickness are present in ail involved organs in scleroderma, The v ascular pathology is associated with altered vascular function with increas ed vasospasm, reduced vasodilatory capacity and increased adhesiveness of t he blood vessels to platelets and lymphocytes, The extent of injury and dys function is reflected by changes in the circulating levels of vascular mark ers. The initial triggers for the vascular pathology are not known. Possibl e viral triggers are visited here, including cytomegalovirus in view of inc reased levels of anti-CMV antibodies in scleroderma, and the remarkable sim ilarities between CMV vasculopathies and scleroderma vascular disease. Endothelial apoptosis in scleroderma may be related to viral infection, imm une reactions to viral or environmental factors, reperfusion injury or to a nti-endothelial antibodies. The impact of the vascular pathology on the evo lution of tissue fibrosis is not known; still, cytokines (TGF beta, IL4), v ascular factors (endothelin), and growth factors (PDGF) are possibly crucia l signals that link the vascular disease to tissue fibrosis, Knowledge of t he regulation of these and other factors wilt provide the opportunity to de velop more rational therapeutic approaches to the disease.