| Endothelial progenitor cells bind and inhibit platelet function and thrombus formation. | |
| | |
MedLine Citation:
|
PMID: 19917882 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: Interactions of endothelial progenitor cells (EPCs) with vascular and blood cells contribute to vascular homeostasis. Although platelets promote the homing of EPCs to sites of vascular injury and their differentiation into endothelial cells, the functional consequences of such interactions on platelets remain unknown. Herein, we addressed the interactions between EPCs and platelets and their impact on platelet function and thrombus formation. METHODS AND RESULTS: Cultured on fibronectin in conditioned media, human peripheral blood mononuclear cells differentiated, within 10 days of culture, into EPCs, which uptake acetylated low-density lipoprotein, bind ulex-lectin, lack monocyte/leukocyte markers (CD14, P-selectin glycoprotein ligand-1, L-selectin), express progenitor/endothelial markers (CD34, vascular endothelial growth factor receptor-2, von Willebrand factor, and vascular endothelial cadherin), and proliferate in culture. These EPCs bound activated platelets via CD62P and inhibited its translocation, glycoprotein IIb/IIIa activation, aggregation, and adhesion to collagen, mainly via prostacyclin secretion. Indeed, this was associated with upregulation of cyclooxygenase-2 and inducible nitric oxide synthase. However, the effects on platelets in vitro were reversed by cyclooxygenase and cyclooxygenase-2 inhibition but not by nitric oxide or inducible nitric oxide synthase inhibition. Moreover, in a ferric chloride-induced murine arterial thrombosis model, injection of EPCs led to their incorporation into sites of injury and impaired thrombus formation, leading to an incomplete occlusion with 50% residual flow. CONCLUSIONS: Peripheral blood mononuclear cell-derived EPCs bind platelets via CD62P and inhibit platelet activation, aggregation, adhesion to collagen, and thrombus formation, predominantly via upregulation of cyclooxygenase-2 and secretion of prostacyclin. These findings add new insights into the biology of EPCs and define their potential roles in regulating platelet function and thrombosis. |
| | |
Authors:
|
Haissam Abou-Saleh; Daniel Yacoub; Jean-Fran??ois Th??or??t; Marc-Antoine Gillis; Paul-Eduard Neagoe; Benoit Labarthe; Pierre Th??roux; Martin G Sirois; Maryam Tabrizian; Eric Thorin; Yahye Merhi |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-11-16 |
Journal Detail:
|
Title: Circulation Volume: 120 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2009 Dec |
Date Detail:
|
Created Date: 2009-12-01 Completed Date: 2010-01-05 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
|
Languages: eng Pagination: 2230-9 Citation Subset: AIM; IM |
Affiliation:
|
Research Center, Montreal Heart Institute and Universit?? de Montr??al, Faculty of Medicine, Montreal, Quebec, Canada, H1T 1C8. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Blood Platelets
/
cytology*,
physiology* Carotid Artery Injuries / physiopathology Cells, Cultured Epoprostenol / secretion Hematopoietic Stem Cells / cytology*, physiology*, secretion Hemostasis / physiology Humans Leukocytes, Mononuclear / cytology Nitric Oxide / metabolism Platelet Adhesiveness / physiology Platelet Aggregation / physiology Regional Blood Flow Thrombosis / physiopathology* |
| Grant Support | |
ID/Acronym/Agency:
|
IAP-73374//Canadian Institutes of Health Research; MOP-82767//Canadian Institutes of Health Research; RMF-79023//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
|
10102-43-9/Nitric Oxide; 35121-78-9/Epoprostenol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The AHR regulates cell cycle progression in human breast cancer cells via a functional interaction w...
Next Document: B-Type Natriuretic Peptides and Cardiovascular Risk. Systematic Review and Meta-Analysis of 40 Prosp...