A number of studies have shown that defects in HO-1 accelerate atherosclerotic lesion formation, preeclampsia and diabetic vascular dysfunction, which usually develop following abnormal elevations of TNF-α, in mouse models and human patients.43, 44, 45 Unfortunately, these studies did not provide evidence that the beneficial effect of HO-1/CO is linked to cross-talk between the NF-κB and eNOS/NO systems. This evidence concerns the gene NOS3 and preeclampsia.