CYBB and endothelial dysfunction: We also found that gp91phox (a major source of superoxide generation) and the lipid peroxidation product, 4-HNE, were dramatically increased in the cerebral cortex of aged rats compared to young animals, and these both contribute to endothelial dysfunction since oxidative damage induced by gp91phox or 4-HNE can impair eNOS function by oxidizing tetrahydrobiopterin (BH4), an essential co-factor for this enzyme’s activity [42, 43].