Early outgrowth cells versus endothelial colony forming cells functions in platelet aggregation

Journal of Translational Medicine

Research

Haissam Abou-Saleh¹  Rahma Boulahya²  Ahmed Hachem²  Younes Zaid²  Olivier Bouchereau²  Lara Bou Khzam³  Yahye Merhi⁴ 

[1] Division of Cardiology, Sidra Medical and Research Center, Doha, Qatar;Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, H1T 1C8, Montreal, QC, Canada;Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, H1T 1C8, Montreal, QC, Canada;Department of Biochemistry, Weill Cornell Medical College in Qatar, Doha, Qatar;Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, H1T 1C8, Montreal, QC, Canada;Faculty of Medicine, Université de Montréal, Montreal, QC, Canada;

关键词: Endothelial progenitor cells;    Platelets;    Aggregation;    Prostacyclin;    Nitric oxide;   

DOI  :  10.1186/s12967-015-0723-6

 received in 2015-06-26, accepted in 2015-11-02,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundEndothelial progenitor cells (EPCs) have been implicated in neoangiogenesis, endothelial repair and cell-based therapies for cardiovascular diseases. We have previously shown that the recruitment of EPCs to sites of vascular lesions is facilitated by platelets where EPCs, in turn, modulate platelet function and thrombosis. However, EPCs encompass a heterogeneous population of progenitor cells that may exert different effects on platelet function. Recent evidence suggests the existence of two EPC subtypes: early outgrowth cells (EOCs) and endothelial colony-forming cells (ECFCs). We aimed at characterizing these two EPC subtypes and at identifying their role in platelet aggregation.MethodsEOCs and ECFCs were generated from human peripheral blood mononuclear cells (PBMCs) seeded in conditioned media on fibronectin and collagen, respectively. The morphological, phenotypical and functional characteristics of EOCs and ECFCs were assessed by optical and confocal laser scanning microscopes, cell surface markers expression, and Matrigel tube formation. The impact of EOCs and ECFCs on platelet aggregation was monitored in collagen-induced optical aggregometry and compared with PBMCs and human umbilical vein endothelial cells (HUVECs). The levels of the anti-platelet agents’ nitric oxide (NO) and prostacyclin (PGI2) released from cultured cells as well as the expression of their respective producing enzymes NO synthases (NOS) and cyclooxygenases (COX) were also assessed.ResultsWe showed that EOCs display a monocytic-like phenotype whereas ECFCs have an endothelial-like phenotype. We demonstrated that both EOCs and ECFCs and their supernatants inhibited platelet aggregation; however ECFCs were more efficient than EOCs. This could be related to the release of significantly higher amounts of NO and PGI2 from ECFCs, in comparison to EOCs. Indeed, ECFCs, like HUVECs, constitutively express the endothelial (eNOS)—and inducible (iNOS)—NOS isoforms, and COX-1 and weakly express COX-2, whereas EOCs do not constitutively express these NO and PGI2 producing enzymes.ConclusionThe different morphological, phenotypic and more importantly the release of the anti-aggregating agents PGI2 and NO in each EPC subtype are implicated in their respective roles in platelet function and thus, may be linked to the increased efficiency of ECFCs in inhibiting platelet aggregation as compared to EOCs.

【 授权许可】

CC BY   
© Bou Khzam et al. 2015