Non-coding RNAs, in particular microRNAs, have recently gained much interest as key regulators of cellular functions. In the vasculature, many miRNAs have been identified that play a role in the endothelium or smooth muscle cells. We have focused on miRNAs that are regulated by fluid shear stress in endothelial cells, as well as miRNAs that are regulated by aging in the cardiovascular system.Using gene set enrichment analysis of microarray expression profiling of shear stress exposed HUVECs, we found that the sequence complementary to the miR-30 seed is enriched in genes that are downregulated by shear stress. Consistently, miR microarray analysis showed that exposure of human umbilical vein ECs (HUVECs) to prolonged laminar shear stress up-regulates all members of the miR-30 family, (1.6- to 2.0-fold, p<0.05). To determine the regulation of miR-30, we overexpressed the shear-induced transcription factor Krüppel-like factor 2 (KLF2). KLF2 overexpression induced a 1.7- to 2.1-fold upregulation of the miR-30 family members (p<0.05). Since miR-30 family members are predicted to affect inflammation associated genes, we further characterized the function of miR-30 family members. Overexpression of miR-30a and -30b in HUVECs by transfection of precursor miRs (Pre-miR) reduced the TNF-α-induced expression of the cell-cell adhesion molecules E-selectin, VCAM1 and ICAM1. Furthermore, miR-30 is predicted to target the 3’UTR of Angiopoietin-2 (Ang2) and overexpression of miR-30 inhibits the expression of Ang2, while miR-30 inhibition using LNA-modified antisense oligonucleotides induces Ang2 expression. KLF2 overexpression also reduces Ang2 levels. Stimulation with recombinant Ang2 alleviates the anti-inflammatory properties of miR-30 overexpression, indicating a causal role of Ang2 for the effects of miR-30.The miR-143/145 family is likewise induced by laminar shear stress in endothelium. We show that miR-143/145 are induced by KLF2 and are secreted in vesicles by endothelial cells. These vesicles are taken up by smooth muscle cells and this induces a contractile phenotype. Injection of miR-143/145-containing vesicles reduces atherosclerosis formation in mice in vivo. Another miRNA that plays a role in smooth muscle cells is miR-29, which is induced by aging and inhibits the expression of extracellular matrix proteins. Inhibition of miR-29 augments extracellular matrix production and reduced age-induced aneurysm formation.