SIMVASTATIN PREVENTS VASCULAR COMPLICATIONS IN THE CHRONIC REACTIVE OXYGEN SPECIES MURINE MODEL OF SYSTEMIC SCLEROSIS

ABSTRACTAims Systemic sclerosis (SSc) is characterized by vasculopathy and organ fibrosis. Although microvascular alterations are very well characterized, structural and functional abnormalities of large vessels are not well defined. Therefore, we evaluated the effect of simvastatin administration on aortic and small renal arteries thickening, and on myofibroblasts differentiation in a murine model of SSc. Methods and results SSc was induced in BALB/c mice by daily subcutaneous injections of hypochlorous acid (HOCl, 100 μl) for 6 weeks. Mice (n = 23) were randomized to receive: HOCl (n = 10); HOCl plus simvastatin (40 mg/kg; n = 8); or vehicle (n = 5). Simvastatin administration started 30 min after HOCl injection, and up to week 6. Aortic and small renal arteries intima–media thickness was evaluated by histological analysis. Immunostaining for α-smooth muscle actin (SMA), vascular endothelial growth factor receptor 2 (VEGFR2), and CD31 in aortic tissues was performed to evaluate myofibroblast differentia...