Mo1891 KLF2 Function on the Pathological Angiogenesis in Patients of Cirrhosis-Induced Portal Hypertension

Abstract

Background & Aims Intrahepatic and splanchnic angiogenesis plays an important role in Portal Hypertension (PHT) caused by cirrhosis. Krupple-like factor 2 (KLF2), a critical angiogenic protective factor, can maintain endothelial cellular phenotype by negatively regulating angiogenesis. Our research is to study whether KLF2 play a role in cirrhosisinduced PHT and its possible mechanism. Methods Human serum samples were collected from 41 PHT patients and 20 healthy subjects, and portal vessel tissue were obtained from 6 PHT patients and 6 cholecystitis controls during their surgeries. Rat models of portal vein ligation (PVL) and CCL4 were also used for our study. The expression of KLF2 and relevant angiogenic factors such asHIF-1α and VEGFwere evaluated. Additionally, human endothelial cells were used for vitro study. Lentivirus was transfected to overexpress KLF2. Tube formation and activation of cells were examined while KLF2 target protein expression were determined. Results We observed a remarkable upregluation of KLF2 in portal vein of PHT patients and angiogenic duodenum of PVL rats compared with controls, accompanied by a significant increasement of some relevant angiogenic factors such as VEGF and HIF-1α in PHT human and rat model. In addition, our vitro experiment observed that stimulated by hypoxia andinflammatory factor, KLF2-overexpressed endothelial cells showed decreased proliferation,migration and vessel tube formation.We also found that, in KLF2-overexpressed cells, KLF2 downstream angiogenic factors such as Ang-2 and NF-κB level were inhibited while eNOS upregulated. Conclusion KLF2 level and angiogenesis were elevated in portal hypertension caused by cirrhosis. KLF2 may suppress the progress of angiogenesis via inhibiting the endothelial cells activation and modulating Ang-2 and NF-κB pathway.