Fig. 8

Gene network analysis in order to identify the association between hypoxia condition and Raynaud disease (RD). According to our results, NO (nitric oxide) and ADMA (Asymmetric dimethylarginine) are considered as signaling pathways thatcontribute in RD. DDAH1 and DDAH2 are two isoforms of DDA that regulate the levels of ADMA in blood. Moreover, ADMA has a negative impact on endothelial-NO synthase 3 (NOS3) and is based on the dysfunction of endothelial cells associated with RD. It was observed that the ARG2 gene (Arginase-2), known as a mitochondria enzyme, contributes in the process of NO production in endothelia cells. The inhibition of NOS3 will lead to the low level of NO production; it can also lead to the increase of oxygen free radical formation and endothelial dysfunction. This figure highlights the importance of relaxation pathways’ block. It has been demonstrated that stress and emotional upsets impact on the severity of the RD