Fig. 5

The influence factors of CYPs and HSD17B in PH. A The influence factors of CYPs in pulmonary hypertension. In patients with PH or animal models, the expression of HIF-2α is increased, and the upregulation of p53 may promote the expression of CYP1B1 and increase the level of 16-OHE. The increased levels of IL-1β and IL-6 may inhibit the activity of CYP3A4 and decrease the level of 2-OHE. The activation of Wnt/β-catenin signaling pathway may promote the expression of CYP1A and increase the level of 2-OHE. The expression of PDE4B is increased leads to decreased levels of cAMP and cGMP, but the content of CYP3A is not clear. The increased expression of CYP2C29 and EET increases the expression of COX-2 through a cAMP-dependent pathway, thereby promoting endothelial cell proliferation and angiogenesis. The increased expression of CYP1B1 may promote the proliferation of PASMCs by increasing the levels of 16α-OHE and cyclin D1, promoting the expression of Nox1, stimulating the irreversible oxidation of protein tyrosine phosphatase, and reducing the activity of nuclear factor Nrf2 and the expression of its antioxidant genes. B The influence factors of HSD17B in PH. Under PH, OSoxidative stress activates the NF-κB channel and promotes of TNF, IL-6, and IL-1 by helper T cell type 1 45, which will upregulate HSD17B1. In addition, in PH, the upregulation of HSD17B1 and the increase of HSD17B1 will increase the production of E2 and decrease the production of E1. Due to TNF, ATRA, and DHT, HSD17B2 increases, resulting in increased E1 production and decreased E2 production. HIF-2α, hypoxia-inducible factor-2alpha; CYP, cytochrome P450; 2-OHE, 2-hydroxyestradiol; PH, pulmonary artery hypertension; OS, oxidative stress; IL, interleukin; PDE4B, phosphodiesterase 4B; cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine 3′:5′-monophosphate; EET, endoscopic eradication therapy; MAP, mitogen-activated protein; COX-2, cyclooxygenase-2; Nox1, nicotinamide adenine dinucleotide phosphate oxidase1; Nrf2, nuclear factor E2-related factor 2; NF-κB, nuclear factor-kappa B; HSD17B, 17β-hydroxysteroid dehydrogenase; TNF, tumor necrosis factor; IGF, insulin-like growth factor