Abstract
Background: Plasminogen Activator inhibitor-1 (PAI-1) is the principle regulator of PA system and its enhanced expression levels are related to many pathological conditions including thrombosis and malignant tumors. We have identified two distinct PAI-1 deficient patients having apparent phenotypes of severe bleeding and impaired wound healing, both of which are not seen in the PAI-1 deficient mice. With employing inducible Pluripotent Stem (iPS) cells established from the patients, we investigated the intrinsic function of PAI-1 in endothelial cells. Methods: iPS cells, generated from PAI-1 deficient patients and control subject, were differentiated to endothelial cells. Endothelial cells were isolated by magnetic sorting with anti-VEGFR-2 antibody, and their functions and the related gene expressions were analyzed. Results: (1) Endothelial cells derived from PAI-1 deficient iPS cells (PAI-1 iPS-ECs) detached more easily from gelatin-coated dishes. (2) PAI-1 iPS-ECs migrated faster in migration assay. (3) Tube formation activities of PAI-1 iPS-ECs, especially vessel branching, were impaired compared with control iPS-ECs. (4) The expression of Dll4 gene, known to be mainly observed at the region of angiogenic-edge, was reduced in PAI-1 iPS-ECs. Conclusion: PAI-1 appeared to play important roles in the function of endothelial cells and to contribute to angiogenesis.
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