VWF and endothelial dysfunction: Some other mechanisms revealed for this event include increased phosphatidyl inositol 3-kinas activity, upregulated inducible nitric oxide synthase, keratin cell signal transduction pathway, nuclear factor k-B, and up-regulated angiotensin II type 1 receptor in vascular smooth muscle cells and direct production of nitric oxide by endothelial cells resulted in increased production of endothelial–1 also increase of von Willebrand factor which is known to be accompanied by endothelial dysfunction (23-27).