This was explained by the research of Abdelghanyet al (2018) which showed that exposure to cigarette smoke has been shown to reduce the BH4 cofactor and correlated with the amount of superoxide and NO production in endothelial cell cultures.34 A decrease of e-NOS and NO level will increase vascular tone, increase expression of adhesion molecules, and trigger coagulation cascade and inflammation.35 In the final pathway, smoking cigarettes leads to increase of aortic intima-medial thickness as an earlier sign of atherosclerosis. Here, NOS3 is linked to atherosclerosis.