This study investigates the expression of microRNAs (miRNAs) in peripheral blood microvesicles from healthy donors. Microvesicles, also known as exosomes or microparticles, are small vesicles that circulate in the peripheral blood and can influence cellular signaling. The researchers hypothesized that under normal conditions, microvesicles contain miRNAs that contribute to biological homeostasis. They isolated microvesicles from the plasma of 51 healthy individuals and profiled the expression of 420 known mature miRNAs using real-time PCR. Hierarchical clustering analysis revealed significant differences in miRNA expression between peripheral blood mononuclear cells (PBMCs) and plasma microvesicles. The study identified 71 co-expressed miRNAs between microvesicles and PBMCs, with 33 and 4 significantly differentially expressed miRNAs in plasma microvesicles and PBMCs, respectively. The predicted gene targets and associated biological pathways regulated by these miRNAs were analyzed, showing that most miRNAs in microvesicles were predicted to regulate cellular differentiation and metabolic pathways, with a few also modulating immune function. This study provides the first characterization of miRNA expression in circulating plasma microvesicles from normal subjects, laying the foundation for future research on the predictive role of peripheral blood miRNA signatures in human diseases.This study investigates the expression of microRNAs (miRNAs) in peripheral blood microvesicles from healthy donors. Microvesicles, also known as exosomes or microparticles, are small vesicles that circulate in the peripheral blood and can influence cellular signaling. The researchers hypothesized that under normal conditions, microvesicles contain miRNAs that contribute to biological homeostasis. They isolated microvesicles from the plasma of 51 healthy individuals and profiled the expression of 420 known mature miRNAs using real-time PCR. Hierarchical clustering analysis revealed significant differences in miRNA expression between peripheral blood mononuclear cells (PBMCs) and plasma microvesicles. The study identified 71 co-expressed miRNAs between microvesicles and PBMCs, with 33 and 4 significantly differentially expressed miRNAs in plasma microvesicles and PBMCs, respectively. The predicted gene targets and associated biological pathways regulated by these miRNAs were analyzed, showing that most miRNAs in microvesicles were predicted to regulate cellular differentiation and metabolic pathways, with a few also modulating immune function. This study provides the first characterization of miRNA expression in circulating plasma microvesicles from normal subjects, laying the foundation for future research on the predictive role of peripheral blood miRNA signatures in human diseases.