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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS. Meshes: Actin Cytoskeleton, Antibodies, Antigens, CD34, Cell Division, Cell Movement, Cell Survival, Cells, Cultured, Chemokine CXCL12, Chemokines, CXC, Cytokines, Endothelial Cells, Fetal Blood, Gene Expression, Hematopoietic Stem Cells, Humans, In Vitro Techniques, Neovascularization, Physiologic, Receptor, PAR-1, Receptors, CXCR4, Up-Regulation.
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Does pAR-1 activation on human late endothelial progenitor cells enhance angiogenesis in vitro with upregulation of the SDF-1/CXCR4 system? Context: The importance of PAR-1 in blood vessel development has been demonstrated in knockout mice. As endothelial progenitor cells (EPCs) are involved in postnatal vasculogenesis, we examined whether they express PAR-1 and whether stimulation by the peptide SFLLRN modulates their angiogenic properties. EPC expanded from human CD34+ cord blood cells expressed PAR-1. PAR-1 activation induced EPC proliferation in a concentration-dependent manner far more potently than that of human umbilical vein endothelial cells. PAR-1 activation also enhanced actin reorganization, promoting both spontaneous migration in a Boyden chamber assay and migration toward SDF-1 and VEGF. As shown by real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR), EPC stimulation by SFLLRN significantly enhanced the mRNA expression of SDF-1 and its receptor CXCR-4. PAR-1 activation also increased CXCR4 expression on EPC and induced SDF-1 secretion, leading to autocrine stimulation. PAR-1 stimulation by SFLLRN also increased the formation of capillary-like structures by EPC in Matrigel, and this effect was abrogated by anti-CXCR-4, anti-SDF-1, and MEK inhibitor pretreatment.
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Human EPCs express functional PAR-1. PAR-1 activation promotes cell proliferation and CXCR4-dependent migration and differentiation, leading to a proangiogenic effect. Final Decision: yes