Background/Purpose. Systemic sclerosis (SSc) is characterized by autoimmunity, widespread microangiopathy, and fibrosis, Vascular endothelial growth factor (VEGF) is the primary inducer and key mediator of angiogenesis; serum levels of the angiogenic factor VEGF are significantly elevated in patients with SSc and correlate with the severity of pulmonary hypertension methods. SSc was induced in BALB/c mice by daily subcutaneous injections of HOCl for 6 weeks reproducing the Cochin oxidant stress model of SSc. Mice (n=24) were randomized in three arms: HOCl (n=10), HOCl plus simvastatin (n=9) and vehicle alone (n=5). Simvastatin treatment was initiated 30 minutes after HOCl subcutaneous injection and continued daily for the 6 weeks. Lung concentrations of VEGF and ERK (extracellular signal-regulated kinase) were analyzed by western blot analyses. Results. Pulmonary VEGF expression is reduced by simvastatin treatment compared to HOCl group (p<0.001). Levels of extracellular signal-regulated kinase (ERK), downstream mediator of VEGF, were also lower in the group of mice treated with simvastatin when compared to HOCl treated mice (p<0.001). Conclusion. Simvastatin reduces the pulmonary expression of VEGF and ERK in the oxidant stress (Cochin) mouse model of SSc. Further studies are needed to measure the potential organspecific effect of statins in vascular remodeling.
SImvastatin treatment downregulates pulmonary expression of vascular endothelial growth factor in a murine model oF systemic sclerosis
BAGNATO, GIANLUCA;BITTO, ALESSANDRA;PIZZINO, CARMELO GABRIELE;IRRERA, NATASHA;SARDO, Maria Adriana;CINQUEGRANI, Maurizio;SQUADRITO, Francesco;ALTAVILLA, Domenica;BAGNATO, Gianfilippo;SAITTA, Antonino
2012-01-01
Abstract
Background/Purpose. Systemic sclerosis (SSc) is characterized by autoimmunity, widespread microangiopathy, and fibrosis, Vascular endothelial growth factor (VEGF) is the primary inducer and key mediator of angiogenesis; serum levels of the angiogenic factor VEGF are significantly elevated in patients with SSc and correlate with the severity of pulmonary hypertension methods. SSc was induced in BALB/c mice by daily subcutaneous injections of HOCl for 6 weeks reproducing the Cochin oxidant stress model of SSc. Mice (n=24) were randomized in three arms: HOCl (n=10), HOCl plus simvastatin (n=9) and vehicle alone (n=5). Simvastatin treatment was initiated 30 minutes after HOCl subcutaneous injection and continued daily for the 6 weeks. Lung concentrations of VEGF and ERK (extracellular signal-regulated kinase) were analyzed by western blot analyses. Results. Pulmonary VEGF expression is reduced by simvastatin treatment compared to HOCl group (p<0.001). Levels of extracellular signal-regulated kinase (ERK), downstream mediator of VEGF, were also lower in the group of mice treated with simvastatin when compared to HOCl treated mice (p<0.001). Conclusion. Simvastatin reduces the pulmonary expression of VEGF and ERK in the oxidant stress (Cochin) mouse model of SSc. Further studies are needed to measure the potential organspecific effect of statins in vascular remodeling.Pubblicazioni consigliate
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