CIRCULATING ENDOTHELIAL PROGENITOR CELLS OF HEALTHY ORIGINS AND PLATELET MICROPARTICLES OF HYPERTENSIVE-HYPERCHOLESTEROLEMIC ORIGINS PLAY OPPOSITE ROLES IN ATHEROSCLEROSIS DEVELOPMENT

Purpose: The study was designed to investigate the role of a cell therapy-based approach, using circulating endothelial progenitor cells (EPCs) and platelet microparticles (PMPs), on atherosclerosis development in... [ view full abstract ]

Purpose: The study was designed to investigate the role of a cell therapy-based approach, using circulating endothelial progenitor cells (EPCs) and platelet microparticles (PMPs), on atherosclerosis development in hypertensive-hypercholesterolemic (HH) hamster model. Consequently, control hamsters received four intravenous inoculations of: (1) EPCs of healthy origins in one dose per month, during four months of diet-induced atherosclerosis, and after HH diet for further four months; (2) EPCs of healthy origins and/or PMPs of HH origins at every other month during HH diet.
Results: EPC treatment had the following effects: (1) reestablished cholesterol/triglyceride concentrations, blood pressure, heart rate, cytokine/chemokine profiles, PMP prothrombotic/EPC paracrine activity; (2) reduced lipid, macrophage, microparticle accumulation and protein expression of proinflammatory molecules into liver and arterial wall; (3) induced the recruitment and incorporation of EPCs into liver and arterial wall; (4) improved arterial dysfunction by increasing contraction/relaxation. PMP transplantation aggravated the above-mentioned biomarkers and atherosclerosis process, which were partially reverted with co-inoculation of PMPs and EPCs.
Conclusions: The study demonstrates that, in an atherosclerotic hamster model, the EPC transplantation ameliorates the diet-induced detrimental effects, while PMP transplantation amplifies the mechanisms involved in the atherosclerotic process development. Our results support the notion that increasing circulating EPC number by different ways could be a promising therapeutic tool for atherosclerosis.
Acknowledgements: This work was supported by grants of the Romanian National Authority for Scientific Research, CNCS–UEFISCDI, project number PN-II-RU-TE-2014-4-0525 and PN-II-RU-TE-2014-4-0523, and by the Romanian Academy. The presentation is dedicated to the 150th anniversary of the Romanian Academy.