Mechanisms of vascular disease

Abstract

Scleroderma (systemic sclerosis (SSc)) is to a large degree identified by the vascular features which may precede the onset of fibrosis by months or even years. Abnormalities in microvessel morphology and vascular dysfunction occur early and evolve into a distinctive vasculopathy that relentlessly advances in nearly all affected organs. This evidence suggests that endothelial cells (ECs) are the primary target in SSc and that the interactions of ECs with other cells and pathways, including cells of both the innate and adaptive immune systems, platelets and coagulation factors, vascular smooth muscle cells and fibroblasts, may take center stage in the disease pathogenesis. Therapeutically, the use of angiotensin-converting enzyme inhibitors for scleroderma renal crisis, endothelin receptor antagonists for pulmonary arterial hypertension (PAH), and phosphodiesterase inhibitors for PAH, Raynaud’s phenomenon, and digital ulcers has significantly improved the care of SSc patients. However, despite a substantial symptomatic improvement, regression of the vascular lesions has been difficult to achieve.