MicroRNA-29a-3p Reduces TNFα-Induced Endothelial Dysfunction by Targeting Tumor Necrosis Factor Receptor 1

Abstract

miR-29a-3p has been shown to be associated with cardiovascular diseases; however, the effect of miR-29a-3p on endothelial dysfunction is unclear. This study aimed to reveal the effects and mechanisms of miR-29a-3p on endothelial dysfunction. The levels of vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and E-selectin were determined by real-time PCR and immunofluorescence staining to reveal the degree of tumor necrosis factor alpha (TNFα)-induced endothelial dysfunction. A luciferase activity assay and cell transfection with a miR-29a-3p mimic or an inhibitor were used to reveal the underlying mechanisms of miR-29a-3p action. Furthermore, the effects of miR-29a-3p on endothelial dysfunction were assessed in C57BL/6 mice injected with TNFα and/or a miR-29a-3p agomir. The results showed that the expression of TNFα-induced adhesion molecules in vascular endothelial cells (EA.hy926 cells, human aortic endothelial cells [HAECs], and primary human umbilical vein endothelial cells [pHUVECs]) and smooth muscle cells (human umbilical vein smooth muscle cells [HUVSMCs]) was significantly decreased following transfection with miR-29a-3p. This effect was reversed by cotransfection with a miR-29a-3p inhibitor. As a key target of miR-29a-3p, tumor necrosis factor receptor 1 mediated the effect of miR-29a-3p. Moreover, miR-29a-3p decreased the plasma levels of TNFα-induced VCAM-1 (32.62%), ICAM-1 (38.22%), and E-selectin (39.32%) in vivo. These data indicate that miR-29a-3p plays a protective role in TNFα-induced endothelial dysfunction, suggesting that miR-29a-3p is a novel target for the prevention and treatment of atherosclerosis.

Extracellular vesicle microRNA cargoes from intermittent hypoxia-exposed cardiomyocytes and their effect on endothelium

“…EV miR-23a-3p from mesenchymal stem cells attenuated myocardial injury through suppressing DMT1 expression [30]. And miR-29a-3p played a protective role in TNFα-induced endothelial dysfunction [31].…”

miR-29a-5p Alleviates Traumatic Brain Injury (TBI)-Induced Permeability Disruption Via Regulating NLRP3 Pathway

“…Ouyang et al revealed the positive role of astrocyteenriched miR-29a in forebrain ischemia (26). Beyond that, miR-29a is also known as a protector in maintaining functions of endothelial cells (29,30). At the same time, peripheral blood miR-29a could be upregulated in patients with severe TBI at a particular time point after injury (31).…”

Secoisolariciresinol Diglucoside Exerts Anti-Inflammatory and Antiapoptotic Effects through Inhibiting the Akt/IκB/NF-κB Pathway on Human Umbilical Vein Endothelial Cells

“…However, anti-inflammatory therapy targeting IL-1 β clearly reduced the incidence of recurrent cardiovascular events by interfering with the innate immune pathway [ 31 ]. Prolonged TNF- α production is associated with endothelial dysfunction [ 32 , 33 ]. Genetically determined reduced IL-6 signaling lowers the risk of multiple cardiovascular disease [ 34 ].…”