Several TFs upregulated in IPAH ECs, including SOX18, STRA13, LYL1,and ELK, have known roles in regulating EC phenotype.SOX18, expressed four times higher in IPAH than control ECs,regulates vasculature development and endothelial barrier integrity.44, –46 In an ovine model ofcongenital heart disease with shunt, SOX18 expression wasupregulated in pulmonary arterial ECs, correlating with increased trans-endothelial resistance.47 Thus, upregulation of SOX18 in IPAH might be a primaryalteration driving EC microangiopathy and obliterative changes, or an adaptivechange to high shear stress. The gene discussed is LYL1; the disease is heart disorder.