Compared with control groups, we found that the expression of Notch1, 3, and 4 decreased, as well as their target genes Hes1 and Hes2, while the expression of Notch2 and extracellular signal-regulated kinase (ERK)1/2 increased in COPD patients compared with controls, as well as in human pulmonary microvascular endothelial cells (HPMECs) when exposed to CS extract (CSE). Here, NOTCH2 is linked to chronic obstructive pulmonary disease.