4.8 Article

MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.0707493105

Keywords

inflammation; nitric oxide; leukocyte; atherosclerosis

Funding

  1. NCI NIH HHS [R01 CA120185] Funding Source: Medline
  2. NHLBI NIH HHS [P01 HL65608, R01 HL074061, P01 HL56091, P01 HL065608, P01 HL056091, R01 HL63706-04, R01 HL063706] Funding Source: Medline

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Adhesion molecules expressed by activated endothelial cells play a key role in regulating leukocyte trafficking to sites of inflammation. Resting endothelial cells normally do not express adhesion molecules, but cytokines activate endothelial cells to express adhesion molecules such as vascular cell adhesion molecule 1 (VCAM-1), which mediate leukocyte adherence to endothelial cells. We now show that endothelial cells express microRNA 126 (miR-126), which inhibits VCAM-1 expression. Transfection of endothelial cells with an oligonucleotide that decreases miR-126 permits an increase in TNF-alpha-stimulated VCAM-1 expression. Conversely, overexpression of the precursor to miR-126 increases miR-126 levels and decreases VCAM-1 expression. Additionally, decreasing endogenous miR-126 levels increases leukocyte adherence to endothelial cells. These data suggest that microRNA can regulate adhesion molecule expression and may provide additional control of vascular inflammation.

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