Circulating endothelial progenitor cell and platelet microparticle impact on platelet activation in hypertension associated with hypercholesterolemia.
OBJECTIVE
The 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.


METHODS
Golden 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.


RESULTS
Compared 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.


CONCLUSIONS
EPCs 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.
Petru Poni' Institute of Macromolecular Chemistry, Iasi, Romania. nicoleta.alexandru@icbp.ro
Nicoleta
N
Alexandru
Doina
D
Popov
Emanuel
E
Dragan
Eugen
E
Andrei
Adriana
A
Georgescu
D000818:Animals; D050197:Atherosclerosis / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology*; D055252:Cell-Derived Microparticles / Q000378:metabolism / Q000473:pathology*; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D054377:Chemokine CXCL12; D006224:Cricetinae; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D006937:Hypercholesterolemia / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006973:Hypertension / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008647:Mesocricetus; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D015539:Platelet Activation; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D039641:Integrin beta Chains; D053583:Interleukin-1beta; D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases