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Exposure to cigarette smoke (Petsophonsakul et al., 2021), and electronic cigarettes ( in vitro cellular studies have shown that constituents of cigarette smoke lead to depletion of the cofactor tetrahydrobiopterin in vascular endothelial cells, which is essential for endothelial NO synthase function, resulting in uncoupling and dysfunction of endothelial NO synthase and endothelial dysfunction ( in vivo studies in smokers and in vitro studies in bovine aortic endothelial cells (Peluffo et al., 2009)