Fig 5.

Proposed disruption of endothelial nitric oxide (NO) synthase (eNOS) pathway in bicuspid aortic valve (BAV) aortopathy. (A) Typically, eNOS produces NO in endothelial cells. NO increases activation of guanylyl cyclase (GC) in smooth muscle cells, leading to phosphorylation of vasodilator-stimulated phosphoprotein (VASP). (B) Under pathologic conditions such as bicuspid aortic valve, eNOS function may become uncoupled from NO synthesis. Production of superoxide anion predominates and NO levels decline. Uncoupled eNOS function can lead to oxidative stress and altered vascular wall remodeling. (BH₄ = tetrahydrobiopterin; cGMP = cyclic guanosine monophosphate; GTP = guanosine 5^’-triphosphate.)