Table 4. Normalized miRNA expression in platelets. detector_name Average Normalized Expression Standard Deviation miR-484 miR-191 miR-146a miR-016 miR-026a miR-126 miR-024 miR-020a miR-019b miR-222 miR-032 miR-486 miR-643 miR-150 miR-096 miR-146b miR-574 miR-140 miR-151 miR-093 miR-183 miR-092 miR-142-3p miR-328 miR-019a miR-030c miR-186 miR-197 miR-030b miR-017-5p miR-331 miR-125a miR-015b miR-126* miR-026b miR-342 miR-628 miR-106a miR-142-5p miR-320 let-7b miR-030a-5p miR-106b miR-182* miR-374 miR-027a miR-030d miR-423 21.079 19.282 14.438 12.851 11.325 10.944 8.910 7.392 7.287 6.626 5.551 4.510 4.391 2.408 2.113 1.936 1.832 1.695 1.607 1.543 1.421 1.418 1.364 1.298 1.195 1.124 1.096 1.092 1.040 1.007 0.930 0.807 0.796 0.752 0.477 0.475 0.413 0.395 0.360 0.330 0.290 0.271 0.247 0.225 0.224 0.203 0.158 0.124 5.936 2.716 4.915 3.097 2.159 4.664 2.883 1.640 2.611 2.071 5.855 3.876 4.507 2.029 3.044 0.538 0.631 0.268 0.670 0.738 2.232 0.581 0.602 0.324 0.514 0.411 0.346 0.447 0.243 0.270 0.312 0.368 0.178 0.291 0.294 0.344 0.431 0.248 0.222 0.149 0.142 0.141 0.185 0.161 0.196 0.160 0.096 0.096 Table 4. cont. detector_name miR-021 miR-195 miR-133b miRNAs in Blood Microvesicles Average Normalized Expression 0.120 0.116 0.104 Standard Deviation 0.111 0.078 0.072 Normalized expression of miRNAs in the platelets (n = 6) was calculated using median normalization analysis then the mean CT value was converted to expression (2^(2DCT)) 6standard deviation (S.D.). doi:10.1371/journal.pone.0003694.t004 percentage of microvesicles derived from endothelial cells. While human endothelial progenitor cells can produce microvesicles in vitro [26], detection of the endothelial derived vesicles in circulation is of interest. We would predict that the endothelial-derived microvesicles may increase upon endothelial cell damage. Recently, elevation of endothelial-derived microvesicles has been reported in patients with pulmonary arterial hypertension [32], however their content is currently unknown. Likewise, the detection of tissue specific miRNAs and microvesicles in the peripheral blood may be a frequent event upon tissue damage. The detection of tumors exosomes (microvesicles) have been found in the peripheral blood to contain miRNAs [41]. Interestingly, comparing this paper’s findings with our data, 18 elevated tumor-derived miRNAs were not detected in the plasma from our normal donors (Table S1). While it has been reported that miRNAs are detected in the plasma [41,42,61–63], this is the first study to profile miRNAs from the plasma microvesicles in a normal healthy population. Since our study was limited to Caucasians, we do not know the influence of race or ethnicity. In this study, we also examined whether miRNA expression in the plasma microvesicles was influenced by age. Surprisingly, we observed no difference between gender and age in our study. These are important factors as we and others examine miRNA expression from the plasma and/or serum in various diseases to serve as diagnostic biomarkers. Our findings indicate that miRNAs circulate in the plasma and PBMC of normal donors. These miRNAs are predicted to regulate homeostasis of hematopoietic cells and of metabolic function. Investigations are currently underway to understand if specific cells are targeted by the plasma microvesicles and determine the influence of these microvesicle-containing miRNA on target cell mRNA expression. We predict that the plasma microvesicles may be selective in their target cells. For instances, platelet-derived microparticles transfer tissue factor to monocytes but not neutrophils [64]. Thus, we predict that the defined function of each subpopulation of the plasma microvesicles and their miRNAs will be important factors in the regulation of immune responses and hematopoiesis. Supporting Information Table S1 Normalized expression for plasma microvesicles and PBMC. Expression of miRNAs in the plasma microvesicles and PBMC were analyzed separately (n = 51). The normalized miRNA expression was generated using median normalization analysis then the mean CT value was converted to expression (2^(2del- taCT)) 6standard deviation (S.D.). Found at: doi:10.1371/journal.pone.0003694.s001 (0.01 MB PDF) Table S2 Predicted targets for miRNAs expressed in the plasma microvesicles and PBMC. Predicted targets were compiled separately using Sanger miRBase and TargetScan for the top PLoS ONE | www.plosone.org 9 November 2008 | Volume 3 | Issue 11 | e3694