THE EFFECTS OF CIRCULATING ENDOTHELIAL PROGENITOR CELL AND PLATELET MICROPARTICLE ADMINISTRATION ON PLATELET-ENDOTHELIAL PROGENITOR CELL INTERPLAY IN ATHEROSCLEROTIC DISEASE

Purpose: In this study we followed the consequences of circulating endothelial progenitor cells (EPCs) and platelet microparticles (PMPs) administration on platelet–EPC interaction in atherosclerosis and the involved... [ view full abstract ]

Purpose: In this study we followed the consequences of circulating endothelial progenitor cells (EPCs) and platelet microparticles (PMPs) administration on platelet–EPC interaction in atherosclerosis and the involved mechanisms. Golden Syrian hamsters were divided in five groups: control (C), hypertensive-hypercholesterolemic (HH), HH treated with EPCs (HH–EPCs) or PMPs (HH–PMPs), HH treated with EPCs and PMPs (HH–EPCs–PMPs).
Results: Compared with C group, EPCs isolated from HH and HH–PMPs groups presented reduced eNOS/VEGF expressions and increased TSP-1, IL-8, MPO, PAI-1 expressions. EPC administration had beneficial effects, while combination with PMPs did not improve EPC influences. Static coincubation of EPCs from HH and HH–PMPs with analogous platelets resulted in increased EPC adhesion/migration, and IL-8, MCP-1, RANTES, MPO, PAI-1 release, explained by platelet hyperaggregability induced by pronounced VASP and actin distribution, and IL-1β,-6,-8, CD40L secretion. EPC therapy alone revealed impaired platelet-EPC interaction directly correlated with inflammatory marker reduction and platelet aggregability.
Conclusions: The present study demonstrates that HH animals revealed EPC and platelet dysfunctions, which correlates with their reduced contribution to re-endothelialisation at the injury site, although in vitro exposure to immobilised platelets promotes their adhesion/migration. EPC administration alone recovers EPC/platelet functions and consolidates their interaction. These findings disclose new advances in understanding the platelet-EPC interaction and its role in the vascular repair.
Acknowledgements: This work was supported by grants of the Romanian National Authority for Scientific Research, CNCS – UEFISCDI, project numbers PN-II-RU-TE-2014-4-0523 and PN-II-RU-TE-2014-4-0525, and by the Romanian Academy. The presentation is dedicated to the 150th anniversary of the Romanian Academy.