Background: SSc is characterized by dysfunction of the vascular tone and microvascular alterations, which are prominent features usually preceding the appearance of clinically detectable fibrosis. The endothelial damage determines blood flow reduction and tissue ischemia. The mechanism leading to selective microvascular injury is unknown. Plasma viscosity and erythrocyte aggregation play a key role in maintaining and regulating microcirculation. Lowering of blood viscosity and increasing erythrocyte aggregation result in an improved blood flow, leading to improved microcirculation, which stands the interactions between rheological factors influencing the hydrodynamic state of blood vessels and the surrounding tissue. Endothelial nitric oxide synthase (eNOS) catalyses the synthesis of nitric oxide (NO), which maintains basal vascular tone and endothelial function. Polymorphisms in gene encoding for e-NOS, impair NO availability, thus affecting plasma NO levels, that may alter vascular tone and red blood cells deformability. Objectives: To evaluate: 1. the relationship between e-NOS gene polymorphisms (T-786C, G894T and 4a/4b) and SSc. 2.The influence of these polymorphisms on the haemorheological profile. Methods: We studied 49 SSc patients (40 female and 9 male, 26 with limited (lSSc) and 23 with diffuse (dSSc) SSc subset) and 122 healthy controls. e-NOS polymorphisms were analysed after genomic DNA extraction from peripheral blood leukocytes, by molecular biology assay. The haemorheological profile has been studied by determination of haematic viscosity, plasmatic viscosity and red cells filtration. Results: A significantly higher prevalence in the allele frequency of the e-NOS gene G894T polymorphism was observed in SSc patients in comparison to controls (p=0.004). A significant association between the e-NOS –786C and 894T, but not e-NOS 4a/4b rare variants, and SSc was found (for the e-NOS C allele: [OR] =11.8; 95% Confidence Interval [CI]: 4.8 to 28.9; p=0.000; for the e-NOS T allele: [OR]= 2.8; 95% Confidence Interval [CI]: 1.3 to 6.0; p=0.009). Moreover e-NOS –786C and 894T rare alleles significantly affected the red cell deformability (for e-NOS C allele: [OR]=3.9; 95% Confidence Interval [CI]= 1.7 to 8.6; p=0.001; for e-NOS T allele: [OR]=2.8; 95% Confidence Interval [CI]= 1.3 to 6.0; p=0.009). Conclusion: eNOS T-786C and G894T polymorphisms influence the predisposition to SSc. The presence of these eNOS rare variants leads to impaired NO availability. These polymorphisms reduces RBC deformability and may be involved in the breakdown of vascular potency in SSc.
|Titolo:||CONTRIBUTION OF RED BLOOD CELLS (RBC) TO VESSEL WALL DAMAGE IN SYSTEMIC SCLEROSIS (SSC)|
|Anno di registrazione:||2005|
|Autori di Ateneo:|
|Autori:||S. Guiducci; C. Fatini; V. Rogai; M. Cinelli; E. Sticchi; L. Mannini; G. Fiori; S. Generini; O. Kaloudi; A. Pignone; R. Abbate; M. Matucci Cerinic|
|Appare nelle tipologie:||1c - Abstract su rivista|