Fig. 1.
Lungs of patients with idiopathic pulmonary fibrosis (IPF) and pulmonary hypertension (PH) have increased expression of hypoxia-inducible factor 1-α (HIF1-α) and HIF2-α within the vascular endothelium. A: representative images of HIF1-α and HIF2-α immunohistochemical staining in a normal patient, in a patient with IPF, and in a patient with IPF and known PH. Scale bars: 50 μm at ×60 magnification. Arrows point to immunostain positive cells. n = 10 per group, except in IPF with PH where n = 4. Quantitative PCR of whole cell lysates of pulmonary microvascular endothelial cells (PMVECs) from normal subjects and patients with IPF and PH exposed to hypoxia (O2 1%) for 6 h, demonstrating increased mRNA expression of HIF1-alpha (B) and HIF2-α (C). D: normal and IPF PMVECs were transiently transfected with an hypoxia response element (HRE)-luciferase reporter and cotransfected with renilla construct and exposed to hypoxia (FiO2 1%) for 24 h. With hypoxia exposure, HRE-luciferase activity was greater in IPF PMVECs compared with normal PMVECs. n = 4 per group. *P < 0.05.