Figure 1.
(A) PHD2 deficiency in endothelial cells and hematopoietic cells induces obliterative vascular remodeling recapitulating the histopathological features of clinical PAH. Representative micrographs of Russel-Movat pentachrome staining demonstrating thickening of the intima, medial, and adventitial, and occlusion of the large and small vessels (black arrowheads) in 3.5 mo. old Egln1Tie2Cre mice (Middle 2). Br, bronchus; V, vessel. Scale bar: 50 μm. Anti-CD31 immunohistochemistry showing multiple-channel lesions positive for the endothelial marker CD31 (red arrows) (Right). Scale bar: 50 μm. Figure adapted with permission from Dai, et al. [17]. (B-E) Factors regulating endothelial cell functions contributing to pulmonary vascular remodeling and PAH. (B) Factors regulating pulmonary EC apoptosis and survival in the pathogenesis of PAH. (C) Factors regulating pulmonary EC proliferation and migration contributing to PAH. (D) Factors affecting pulmonary EC metabolism (glycolysis switch) and epigenetic regulation. (E) Factors regulating EndoMT contributing to PAH. Abbreviations: AMPK, AMP-activated protein kinase; BMPR2, bone morphogenic protein receptor 2; Cav1, caveolin 1; CLIC4, chloride intracellular channel 4; FGF2, fibroblast growth factor 2; GDF11, growth differentiation factor 11; GrzB, granzyme B; HIF2α, hypoxia-inducible factor 2α; HIMF, hypoxia-induced mitogenic factor; IL, interleukin; ITSN 1s, intersectin 1 short; MEF2, myocyte enhancer factor 2; miRNA, micro RNA; mTOR, mammalian target of rapamycin; Nep, neprilysin; PCD4, programmed cell death 4; PDGFB, platelet-derived growth factor-BB; PHD2, prolyl hydroxylase 2; PI3K, phosphoinositide 3-kinase; PPARγ, peroxisome proliferator-activated receptor γ; PTPL1, protein tyrosine phosphatase; TGFβ, transforming growth factor β; VEGF, vascular endothelial growth factor.