Effect of Vasodilator And Immunosuppressive Therapy On The Endothelial Dysfunction In Patients With Systemic Sclerosis

Background: A comparative analysis of flow-mediated-vasodilation (FMD), vasoactive angiogenic, and fibrogenic mediators between treatment-naive and treated Systemic sclerosis (SSc) patients is an unmet need.Aim and Objective: 1) To assess the FMD and different pathogenic mediators in SSc patients [treatment naïve (Group-I, n=24) on vasodilator (Group-II, n=10), on vasodilator + immunosuppressive (Group-III, n=22)], and in healthy control (HC), n= 20]. To assess the proportion of circulating Endothelial cells in Group-I.Materials and method: FMD was measured in all the participants. Serum levels of NO, ET1, NO/ET1, sVCAM, sICAM, TGFβ, IL-6, VEGF were measured along with the gene expressions of eNOS, iNOS, ET-1, TGFβ. CEC was measured in Group-I and HC. Results: FMD was significantly decreased in all SSc patients though receiving treatment.Upregulation of serum NO and ET concentrations were noted post-treatment with an unaltered NO/ET1 ratio. NO was positively correlated with FMD (r= 0.6), and negatively with TGFβ (r=-0.5). ET-1 showed less correlation with TGFβ (r=-0.5) but no significant correlation with FMD. Circulating endothelial cell (CEC) was significantly higher in Group-I (3.2%) than HC (0.8%) (p = 0.002), and it showed a good correlation with NO (r=-0.7, p=0.0001) and NO/ET1 (r=-0.6,p=0.007).Conclusion: Endothelial dysfunction was seen in SSc patients irrespective of treatment which might be due to the unaltered NO/ET1. NO might be the major driving molecule in the vascular pathophysiology of SSc.