MicroRNAs (miRNAs) are post-transcriptional inhibitors of gene expression, which act by provoking either the degradation or functional inhibition of their mRNA targets.11 The interaction between a miRNA and its targeted mRNAs happens within the RNA-induced silencing complex (RISC), which includes the Argonaute-2 (AGO-2) protein and the enzyme Dicer. Dicer also executes the final maturation step in miRNA biogenesis.11 miRNAs contribute to cardiovascular development, homeostasis, and disease.11 miRNAs can be released in biologically active forms by the parental cells, and they are stable in biological fluids, thus representing novel biomarker candidates.12 In fact, resilience of extracellular miRNAs is granted through different partnerships, such as with extracellular vesicles (EVs), lipoprotein complexes, and RNA-binding proteins or protein complexes, including AGO-2.11 Exosomes are the smallest (∼30–120 nm in size) of the known endogenous EVs. Exosomes have an endosomal origin and are retained within the multivesicular bodies (MVBs) as a result of endosome compartmentalization, being released when the latter fuse with the cell membrane.13 Exosomal miRNAs can be taken-up by non-parental cells, thus influencing their gene expression and ultimately working as cell-to-cell messengers in local and distant micro-communication mechanisms.11 The presence of miRNAs in the PF has been recently described.10 However, whether the PF miRNAs are of cardiac origin, if they are released via EVs, and their functional relevance have remained unaddressed.