MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1 (VCAM-1). This study shows that endothelial cells express miR-126, which inhibits VCAM-1 expression. Transfection of endothelial cells with an oligonucleotide that decreases miR-126 levels increases TNF-α-stimulated VCAM-1 expression, while overexpression of miR-126 decreases VCAM-1 expression. Decreasing endogenous miR-126 levels increases leukocyte adherence to endothelial cells, suggesting that miR-126 regulates adhesion molecule expression and may provide additional control of vascular inflammation. VCAM-1 is an intercellular adhesion molecule expressed by endothelial cells and mediates leukocyte adhesion by interacting with its α4β1 integrin ligand, very late antigen 4 (VLA-4). VCAM-1 expression is regulated primarily at the level of transcription, but posttranscriptional regulation is also possible. The study hypothesizes that an endogenous miRNA regulates VCAM-1 expression and vascular inflammation. miRNAs are small noncoding RNAs that regulate target genes posttranscriptionally. miR-126 is selectively expressed in endothelial cells and is a potential regulator of VCAM-1 expression. The study shows that miR-126 suppresses VCAM-1 expression, thereby decreasing leukocyte interactions with endothelial cells. miR-126 binds to a region in the 3'-UTR of the VCAM-1 transcript, which regulates VCAM-1 expression. The study also shows that miR-126 regulates VCAM-1 expression through a miR-126-binding site in the VCAM-1 3'-UTR. Exogenous miR-126 decreases leukocyte adherence to endothelial cells, while endogenous miR-126 inhibits leukocyte adherence through the regulation of VCAM-1. The study concludes that miR-126 inhibits VCAM-1 expression and limits leukocyte adherence to endothelial cells. miRNA can regulate expression of adhesion molecules and regulate vascular inflammation. The study also highlights the role of miRNA in endothelial biology and the potential for miRNA to regulate vascular inflammatory pathways. The study provides insights into the regulation of miR-126 expression and its role in endothelial biology.MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1 (VCAM-1). This study shows that endothelial cells express miR-126, which inhibits VCAM-1 expression. Transfection of endothelial cells with an oligonucleotide that decreases miR-126 levels increases TNF-α-stimulated VCAM-1 expression, while overexpression of miR-126 decreases VCAM-1 expression. Decreasing endogenous miR-126 levels increases leukocyte adherence to endothelial cells, suggesting that miR-126 regulates adhesion molecule expression and may provide additional control of vascular inflammation. VCAM-1 is an intercellular adhesion molecule expressed by endothelial cells and mediates leukocyte adhesion by interacting with its α4β1 integrin ligand, very late antigen 4 (VLA-4). VCAM-1 expression is regulated primarily at the level of transcription, but posttranscriptional regulation is also possible. The study hypothesizes that an endogenous miRNA regulates VCAM-1 expression and vascular inflammation. miRNAs are small noncoding RNAs that regulate target genes posttranscriptionally. miR-126 is selectively expressed in endothelial cells and is a potential regulator of VCAM-1 expression. The study shows that miR-126 suppresses VCAM-1 expression, thereby decreasing leukocyte interactions with endothelial cells. miR-126 binds to a region in the 3'-UTR of the VCAM-1 transcript, which regulates VCAM-1 expression. The study also shows that miR-126 regulates VCAM-1 expression through a miR-126-binding site in the VCAM-1 3'-UTR. Exogenous miR-126 decreases leukocyte adherence to endothelial cells, while endogenous miR-126 inhibits leukocyte adherence through the regulation of VCAM-1. The study concludes that miR-126 inhibits VCAM-1 expression and limits leukocyte adherence to endothelial cells. miRNA can regulate expression of adhesion molecules and regulate vascular inflammation. The study also highlights the role of miRNA in endothelial biology and the potential for miRNA to regulate vascular inflammatory pathways. The study provides insights into the regulation of miR-126 expression and its role in endothelial biology.