Circulating Endothelial Progenitor Cell and Platelet Microparticle Impact on Platelet Activation in Hypertension Associated with Hypercholesterolemia

Abstract

AimThe purpose of this project was to evaluate the influence of circulating endothelial progenitor cells (EPCs) and platelet microparticles (PMPs) on blood platelet function in experimental hypertension associated with hypercholesterolemia.MethodsGolden Syrian hamsters were divided in six groups: (i) control, C; (ii) hypertensive-hypercholesterolemic, HH; (iii) ‘prevention’, HHin-EPCs, HH animals fed a HH diet and treated with EPCs; (iv) ‘regression’, HHfin-EPCs, HH treated with EPCs after HH feeding; (v) HH treated with PMPs, HH-PMPs, and (vi) HH treated with EPCs and PMPs, HH-EPCs-PMPs.ResultsCompared to HH group, the platelets from HHin-EPCs and HHfin-EPCs groups showed a reduction of: (i) activation, reflected by decreased integrin 3β, FAK, PI3K, src protein expression; (ii) secreted molecules as: SDF-1, MCP-1, RANTES, VEGF, PF4, PDGF and (iii) expression of pro-inflammatory molecules as: SDF-1, MCP-1, RANTES, IL-6, IL-1β; TFPI secretion was increased. Compared to HH group, platelets of HH-PMPs group showed increased activation, molecules release and proteins expression. Compared to HH-PMPs group the combination EPCs with PMPs treatment induced a decrease of all investigated platelet molecules, however not comparable with that recorded when EPC individual treatment was applied.ConclusionEPCs have the ability to reduce platelet activation and to modulate their pro-inflammatory and anti-thrombogenic properties in hypertension associated with hypercholesterolemia. Although, PMPs have several beneficial effects in combination with EPCs, these did not improve the EPC effects. These findings reveal a new biological role of circulating EPCs in platelet function regulation, and may contribute to understand their cross talk, and the mechanisms of atherosclerosis.

Microparticles of healthy origins improve endothelial progenitor cell dysfunction via microRNA transfer in an atherosclerotic hamster model

“…There were no differences in weight between the studied animal groups. These results were correlated with those obtained in our previously papers on the same experimental diet model of atherosclerosis …”

Dysfunctional Endothelial Progenitor Cells in Cardiovascular Diseases

“…54,55 There is evidence that chronic exposure to increased plasma cholesterol levels could attenuate the repair of lipoprotein-mediated endothelial injury, possibly by reducing the availability and function of circulating EPCs. 57 These findings reveal a new biological role of circulating EPCs in platelet function regulation, which may contribute to their role in repair of endothelial injury due to hyperlipidemia. 57 These findings reveal a new biological role of circulating EPCs in platelet function regulation, which may contribute to their role in repair of endothelial injury due to hyperlipidemia.…”

Effects of transplanted circulating endothelial progenitor cells and platelet microparticles in atherosclerosis development

“…Here, we demonstrate the PMP/EPC contribution towards vascular dysfunction and atherosclerotic plaque progression/regression in vivo (Figure ). Because the HH hamster model has been extensively used in our previous studies to evaluate the pathophysiology of atherosclerosis (Alexandru et al., 2011; Georgescu et al., , Alexandru et al.,; Georgescu et al., ), we considered that this could be a useful tool to examine the involvement of PMPs/EPCs in atherosclerosis.…”