For example, upon chronic CS exposure, CDDO-Im induces a more significant upregulation of Nrf2 and its target genes, mitigating CS-induced lung oxidative stress, tissue destruction, and even pulmonary hypertension in wild-type mice; however, these protective effects are not obviously observed in Nrf2-deficient mice. This evidence concerns the gene NFE2L2 and pulmonary arterial hypertension.