title: Effects of transplanted circulating endothelial progenitor cells and platelet microparticles in atherosclerosis development.
abstract: BACKGROUND
  Atherosclerosis is an inflammatory disease, in which risk factors such as hyperlipidemia and hypertension affect the arterial endothelium, resulting in dysfunction, cell damage or both. The number of circulating endothelial progenitor cells and microparticles provides invaluable outcome prediction for atherosclerosis disease. However, evidence for the therapeutic potential of endothelial progenitor cells and microparticles in atherosclerosis development is limited. Our study was designed to investigate the possible protective role of a cell therapy-based approach, using endothelial progenitor cells and the dual behaviour of circulating platelet microparticles, on atherosclerosis development in hypertensive-hypercholesterolemic hamster model. Consequently, control hamsters received four intravenous inoculations of: (1) 1×10(5) endothelial progenitor cells of healthy origins in one dose per month, during four months of diet-induced atherosclerosis, and after hypertensive-hypercholesterolemic diet for further four months; (2) in a second set of experiments, 1×10(5) endothelial progenitor cells of healthy origins or/and 1×10(5) platelet microparticles of atherosclerotic origins were inoculated every other month during hypertensive-hypercholesterolemic diet.
  
  
  RESULTS
  Endothelial progenitor cell treatment had the following effects: (1) re-established plasmatic parameters: cholesterol and triglyceride concentrations, blood pressure, heart rate, cytokine and chemokine profiles, platelet microparticle pro-thrombotic activity and endothelial progenitor cell paracrine activity reflected by cytokine/chemokine detection; (2) reduced lipid, macrophage and microparticle accumulation in liver; (3) reduced atherosclerosis development, revealed by decreased lipid, macrophage and microparticle content of arterial wall; (4) induced the recruitment and incorporation of endothelial progenitor cells into liver and arterial wall; (5) improved arterial dysfunction by increasing contraction and relaxation; (6) reduced the protein expression of specific pro-inflammatory molecules in liver and arterial wall. Platelet microparticle transplantation aggravated the above-mentioned biomarkers and atherosclerosis process, which were partially reverted with co-inoculation of platelet microparticles and endothelial progenitor cells.
  
  
  CONCLUSIONS
  With this study, we demonstrate in a hypertensive-hypercholesterolemic hamster model, that the endothelial progenitor cell-based therapy suppresses the development of atherosclerosis and reduces hepatic lipid and macrophage accumulation with the consequent alleviation of dyslipidaemia and hypertension.
  
  
  CONCLUSIONS
  Our results support the notion that increasing the number of circulating endothelial progenitor cells by different ways could be a promising therapeutic tool for atherosclerosis.
authors.affiliation: Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of Romanian Academy, Bucharest, Romania.|Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Adriana
authors.initials: A
authors.lastname: Georgescu
authors.affiliation: Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of Romanian Academy, Bucharest, Romania.|Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Nicoleta
authors.initials: N
authors.lastname: Alexandru
authors.affiliation: Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of Romanian Academy, Bucharest, Romania.
authors.forename: Eugen
authors.initials: E
authors.lastname: Andrei
authors.affiliation: Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of Romanian Academy, Bucharest, Romania.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Dragan
authors.affiliation: Faculty of Medicine, 'Titu Maiorescu' University, Bucharest, Romania.|General Surgery Clinic, CF 2 Clinical Hospital, Bucharest, Romania.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cochior
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Sérgio
authors.initials: S
authors.lastname: Dias
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000473:pathology / Q000628:therapy; D001792:Blood Platelets / Q000378:metabolism*; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D006224:Cricetinae; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*
keywords: Atherosclerosis; Cell therapy; Circulating platelet microparticles (PMPs); Endothelial progenitor cells (EPCs); Vascular dysfunction