PMID- 19252096 OWN - NLM STAT- MEDLINE DCOM- 20090619 LR - 20220224 IS - 0363-6135 (Print) IS - 1522-1539 (Electronic) IS - 0363-6135 (Linking) VI - 296 IP - 5 DP - 2009 May TI - Release of proinflammatory mediators and expression of proinflammatory adhesion molecules by endothelial progenitor cells. PG - H1675-82 LID - 10.1152/ajpheart.00665.2008 [doi] AB - Cell therapy with endothelial progenitor cells (EPCs) is an emerging therapeutic option to promote angiogenesis or endothelial repair. Although the release of angiogenic paracrine factors is known to contribute to their therapeutic effect, little is known about their release of proinflammatory factors and expression of proinflammatory adhesion molecules. "Early" EPCs and "late" EPCs were isolated from human peripheral blood and their release of chemokines and thromboinflammatory mediators as well as their expression of the proinflammatory adhesion molecules was assessed at baseline and with stimulation. The effect of simvastatin on monocyte chemoattractant protein-1 (MCP-1) secretion by late EPCs from patients with vascular disease was also evaluated. All groups of EPCs released chemokines and thromboinflammatory mediators. Early EPCs primarily released thromboinflammatory mediators such as tissue factor (0.5 +/- 0.1 ng/million cells, P < 0.05), whereas adult late EPCs primarily released chemokines such as MCP-1 (287 +/- 98 ng/million cells, P < 0.05). Stimulation with tumor necrosis factor (TNF)-alpha augmented the expression of proinflammatory adhesion molecules and paracrine factors by all EPC subtypes. The release of MCP-1 by late EPCs was markedly reduced by simvastatin treatment of the cells. All EPC subtypes expressed proinflammatory paracrine factors and adhesion molecules involved in atherosclerosis. Future clinical studies should therefore not only assess the efficacy of EPCs but also monitor inflammatory activation following EPC transplantation in patients. Pharmacological modulation of EPCs before and after transplantation may represent a novel approach to improve their safety. FAU - Zhang, Yanmin AU - Zhang Y AD - Univ. of Chicago, Pritzker School of Medicine, 5841 South Maryland Ave, Mail-Code 6080, Chicago, IL 60637, USA. FAU - Ingram, David A AU - Ingram DA FAU - Murphy, Michael P AU - Murphy MP FAU - Saadatzadeh, M Reza AU - Saadatzadeh MR FAU - Mead, Laura E AU - Mead LE FAU - Prater, Daniel N AU - Prater DN FAU - Rehman, Jalees AU - Rehman J LA - eng GR - K08 HL080082-04/HL/NHLBI NIH HHS/United States GR - K08 HL080082/HL/NHLBI NIH HHS/United States GR - K08 HL080082-01A1/HL/NHLBI NIH HHS/United States GR - K08 HL080082-03/HL/NHLBI NIH HHS/United States GR - K08 HL080082-02/HL/NHLBI NIH HHS/United States GR - K08-HL080082/HL/NHLBI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20090227 PL - United States TA - Am J Physiol Heart Circ Physiol JT - American journal of physiology. Heart and circulatory physiology JID - 100901228 RN - 0 (CCL2 protein, human) RN - 0 (CCL5 protein, human) RN - 0 (CXCL8 protein, human) RN - 0 (Cell Adhesion Molecules) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL5) RN - 0 (Chemokines) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Inflammation Mediators) RN - 0 (Interleukin-8) RN - 0 (Platelet Endothelial Cell Adhesion Molecule-1) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 9035-58-9 (Thromboplastin) RN - AGG2FN16EV (Simvastatin) RN - EC 3.1.3.48 (Leukocyte Common Antigens) RN - EC 3.1.3.48 (PTPRC protein, human) SB - IM MH - Adult MH - Adult Stem Cells/drug effects/*immunology MH - Cell Adhesion Molecules/*metabolism MH - Cell Proliferation MH - Cells, Cultured MH - Chemokine CCL2/metabolism MH - Chemokine CCL5/metabolism MH - Chemokines/*metabolism MH - Endothelial Cells/drug effects/*immunology MH - Fetal Stem Cells/drug effects/*immunology MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology MH - Inflammation Mediators/*metabolism MH - Intercellular Adhesion Molecule-1/metabolism MH - Interleukin-8/metabolism MH - Leukocyte Common Antigens/metabolism MH - *Paracrine Communication MH - Phenotype MH - Platelet Endothelial Cell Adhesion Molecule-1/metabolism MH - Simvastatin/pharmacology MH - Thromboplastin/metabolism MH - Tumor Necrosis Factor-alpha/metabolism MH - Vascular Cell Adhesion Molecule-1/metabolism PMC - PMC2685352 EDAT- 2009/03/03 09:00 MHDA- 2009/06/20 09:00 PMCR- 2010/05/01 CRDT- 2009/03/03 09:00 PHST- 2009/03/03 09:00 [entrez] PHST- 2009/03/03 09:00 [pubmed] PHST- 2009/06/20 09:00 [medline] PHST- 2010/05/01 00:00 [pmc-release] AID - 00665.2008 [pii] AID - H-00665-2008 [pii] AID - 10.1152/ajpheart.00665.2008 [doi] PST - ppublish SO - Am J Physiol Heart Circ Physiol. 2009 May;296(5):H1675-82. doi: 10.1152/ajpheart.00665.2008. Epub 2009 Feb 27.