Endothelin-1 Levels in Scleroderma Patients: A Pilot Study

Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor, which mediates vascular wall cells proliferation, fibrosis, and inflammation through two types of ET-1 receptors (ET-A and ET-B). In our retrospective study the serum levels of ET-1 in 18 systemic sclerosis (SSc) patients with and without digital ulcers (DUs) were assessed to observe possible correlation between the levels of ET-1, the evolution of SSc, and the therapy with an ET-1 antagonist (bosentan). In all our patients, the levels of ET-1 were found higher than normal range and correlate with the severity of the disease. Furthermore we also observed that in patients without DUs the levels of ET-1 were higher and did not correlate with new DUs development. In conclusion, the levels of ET-1 in our studied patients do not correlate with the possible development of DUs. The reduction of ET-1 levels in DUs patients in therapy with bosentan confirms the efficacy of this molecule both for treatment and prevention of digital ulcers. The inhibition of ET-A receptor by its antagonist may activate the opposite ET-B receptors, with well-known function ET-1 degradation and reducing of ET-1 serum level as confirmed in our pilot study. 1. Introduction Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vascular involvement and fibrosis of different tissues and organs. Approximately 50% of patients with SSc develop digital ulcers (DUs) during the course of the disease [1]. An important role in the pathogenesis of SSc is played by the endothelins and in particular by endothelin 1 (ET-1). ET-1 is a potent endogenous vasoconstrictor, which also mediates vascular wall cells proliferation, fibrosis, and inflammation, mainly synthesized in endothelial cells with autocrine and paracrine effects. There are two types of ET-1 receptors: ET-A and ET-B. ET-A receptors are expressed by vascular smooth muscle cells and mediate vasoconstriction. ET-B receptors are mainly expressed on endothelial cells and mediate vasodilatation. In SSc patients, ET-B receptors are downregulated. This fact may displace the balance towards vasoconstriction and fibrosis [2]. The aim of our retrospective study was to assess the serum levels of ET-1 in SSc patients with and without digital ulcers, in order to observe a possible correlation between the levels of ET-1 and the evolution of SSc. In addition, we evaluated the efficacy of the bosentan, a dual ET-1 receptor antagonist licensed for the management of pulmonary arterial hypertension (PAH) and the prevention of DUs [3]. 2. Methods 2.1. Subjects