Abstract

Systemic Sclerosis (SSc) is a multisystem connective tissue disease of unknown etiology that is characterized by inflammation, vascular dysfunction and fibrosis of the skin and visceral organs. SSc is clinically diverse both in terms of the burden of skin and organ involvement and the rate of progression of the disease. Recent studies indicate that the endothelin system, especially ET-1 and the ETA and ETB receptors may play a key role in the pathogenesis of SSc. A new class of drugs, endothelin receptor antagonists has been introduced for treatment of patients with pulmonary arterial hypertension (PAH). Bosentan, a dual endothelin receptor antagonist as well as Sitaxsentan and Ambrisentan, selective blockers of the ETA receptor have proven effective in SSc-PAH. This effect may be mediated through both a vasodilatory and antifibrotic effect, thus making these agents attractive as potential disease modifying agents for SSc.

Keywords: Systemic sclerosis, scleroderma, endothelin receptor antagonists, bosentan, ambrisentan, sitaxsentan, fibrosis, heterogeneous autoimmune, blood vessels, visceral organs, endothelial injury, immune activation, extracellular matrix, skin, gastrointestinal tract, skeletal muscles, kidneys, heart, autoantibodies, anticentromere antibodies, antitopoisomerase I, endothelial dysfunction, infections, oxidative stress, proliferation, vasoconstrictors, vasodilators, vasoactive peptides, nitric oxide, vasodilatory, bronchoalveolar lavage (BAL), ischemic digital ulcers, vasculopathy, metalloproteinases, peribronchiolar, rodents mimics idiopathic, placebo, myocardial perfusion, Tissue-Doppler echocardiography, vasodilation, Raynaud's phenomenon, ulceration, vascular ectasia, scleroderma renal crisis, obliteration, retrospective study, dyspnea, pulmonary artery catheter, prostacyclin, hypertrophy, pulmonary hypertension, rheumatologic diseases