HMOX1 and endothelial dysfunction: Finally, uremic toxins are well-known inducers of endothelial dysfunction, which is mediated by increased reactive oxygen species production and downregulation of antioxidant genes such as Nrf-2, α-Klotho, and Heme oxygenase-1 and have been implicated as proinflammatory mediators of endothelial dysfunction (38).