Mechanisms of vascular disease

Abstract

Scleroderma (systemic sclerosis, SSc) is to a large degree identified by the vascular features, particularly in the early stages of the disease. Disorganized microvasculature and vascular dysfunction occur early and evolve into a distinctive vasculopathy that relentlessly advance in many organs. The fact that the vascular manifestations consistently precede tissue fibrosis suggests that endothelial cells (ECs) are the primary target in this disease, and that ECs interaction with other cells and pathways, including the innate and adaptive immune system, platelets and coagulation factors, smooth muscle cells, and fibroblasts underlie the 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 infarction have significantly improved the care of SSc patients. Still, and despite this symptomatic improvement, regression of the vascular lesions has been difficult to achieve. Clinically, the vascular manifestations in SSc include Raynaud's phenomenon, the early edematous puffy hands, telangiectasias, digital ulcers, PAH, myocardial dysfunction, and scleroderma renal crisis.