NOS3 and endothelial dysfunction: Leptin supplementation into mice that did not have leptin showed a significantly increased miR21 levels, and decreased NOS3 phosphorylation (NOS3-p/NOS3 ratio of 2.1) (Fig. 3D and 3E) as compared to leptin knockout mice, thus firmly establishing that leptin induced miR21-mediated NOS3 phosphorylation, at least in part, plays a role in the sinusoidal endothelial dysfunction that might result from decreased NO bioavailability due to decreased NOS3 phosphorylation.