Abstract
Aim: The aim of this study was to analyze the expressed profiles of miRNAs in plasma, platelets, and platelet-derived microvesicles (PMVs) obtained from experimental induced atherosclerosis animal model and to investigate the effect of EPC transplantation on these profiles.Methods: Seventeen selected circulating miRNAs (miR-19a,-21,-126,-146a,-223,-26b,-92a,-222,-210,-221,-143,-10a,-145,-155,-34a,-204, and miR-214) were individually analyzed in plasma, platelets, and PMVs isolated from peripheral blood of hypertensive-hyperlipidemic hamsters treated or not with endothelial progenitor cells (EPCs), and of healthy hamsters taken as control group.Results: Comparative with control group, in hypertension associated with hyperlipidemia the investigated miRNA expression profiles were different: (i) in plasma, the levels of all investigated miRNAs were significantly increased, the highest enhances being noticed for miR-21,-146a,-221,-143,-34a, and miR-204; (ii) in platelets, the expressions of almost all miRNAs were significantly elevated, remarkable for miR-126,-146a,-223,-222, and miR-214, while levels of miR-143, miR-10a, and miR-145 were significantly reduced; (iii) in PMVs, numerous miRNAs were found to have significantly increased levels, especially miR-222,-221,-210, and miR-34a, whereas expressions of various miRNAs as miR-223,-214,-146a,-143,-10a, and miR-145 were significantly decreased. The treatment with EPCs had the following reverse effects: (i) in plasma, significantly reduced the expression of miR-26b,-143,-34a,-204, and miR-214; (ii) in platelets, significantly decreased the levels of almost investigated miRNAs, with remarkably diminishing for miR-126 and miR-221; and (iii) in PMVs, significantly lowered the expression of some miRNAs, with considerably reductions for miR-222,-221,-210, and miR-19a, while the level of miR-214 was found elevated.Conclusions: The present study revealed that miRNAs have differential expression profiles in plasma, platelets, and PMVs under hypertension associated with hyperlipidemia conditions. The different miRNA profile in PMVs compared with platelets indicated an active mechanism of selective packing of miRNAs into PMVs from maternal cells; various miRNAs such as miR-19a,-21,-126,-26b,-92a,-155,-204,-210,-221,-222, and−34a delivered by PMVs may contribute to enrichment of circulating plasma miRNA expression. In addition, our study showed that the EPC-based therapy can regulate the expressions of investigated miRNAs into the three sources. These results provide novel information that could help in finding potential targets for the development of new therapeutic strategies in the cardiovascular disease.
Highlights
Atherosclerosis is a chronic immune-inflammatory disorder that integrates multiple cell types and a diverse set of inflammatory mediators [1]
As our purpose was to investigate the miRNA profiles with key role in the cardiovascular disease (CVD) development in plasma, platelets, and PMVs obtained in peripheral blood collected from hypertensivehyperlipidemic hamster (HH group; which could mimic human atherosclerosis), we individually quantified several miRNAs employing hybridization probes in each investigated sample
We explored the changes induced by Endothelial progenitor cells (EPCs) transplantation on profiles of these miRNAs in plasma, platelets, and PMVs from HH group injected with EPCs (HH-EPCs group)
Summary
Atherosclerosis is a chronic immune-inflammatory disorder that integrates multiple cell types and a diverse set of inflammatory mediators [1]. The discovery of miRNAs and their role in the regulation of gene expression in humans is one of the most exciting scientific discoveries in the last years. Gene regulation modulated by miRNAs is involved in almost biological processes in mammals and has important roles in health and disease states [1]. Expressions of circulating miRNAs have been described to be associated with cardiovascular disease (CVD): miRNA-19, miRNA-21, miRNA126, miRNA-146, and miRNA-223 [4]; with coronary artery disease (CAD): miRNA-92a, miRNA-221, and miRNA-222 [5] and with hypertension, miR-143 [5]. Due to its involvement to the pathogenesis of various human disorders, miR-214 has been regarded as a promising marker in the prognosis, diagnosis and treatment of CVD [7]
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