One of the major mechanisms that have been shown to be involved in systemic endothelial dysfunction in diabetes is an impairment of signal transduction or substrate availability of NO33,34, which contrasts with our data that shows increased NO levels in plasma and in HFHSu aorta samples (Fig. 4a).The source of these increased NO levels is the augmented expression of iNOS and eNOS (Fig. 4b–c), reflecting an inflammatory-induced NO production. The gene discussed is NOS3; the disease is endothelial dysfunction.