Forkhead Box C2 Attenuates Lipopolysaccharide-Induced Cell Adhesion via Suppression of Intercellular Adhesion Molecule-1 Expression in Human Umbilical Vein Endothelial Cells

Abstract

Atherosclerosis is a chronic vascular inflammatory disease that involves diverse cell types and circulating regulatory factors, including intercellular adhesion molecule (ICAM)-1, a proinflammatory cytokine. Lipopolysaccharides (LPS) increase ICAM-1 expression and promote cell adhesion, but the mechanism is not clear. We found that LPS induced time-and dose-regulated upregulation of ICAM-1 expression and downregulation of forkhead box protein C2 (Foxc2) expression in human umbilical vein endothelial cells (HUVECs). Overexpression of Foxc2 significantly inhibited both LPS-induced ICAM-1 expression in HUVECs and LPS-induced adhesion of THP-1 cells to HUVECs. Foxc2 siRNA dramatically increased both LPS-induced ICAM-1 expression and LPS-induced adhesion of THP-1 human monocytes cells to HUVECs. We conclude that Foxc2 inhibited LPS-induced adhesion of THP-1 cells to HUVECs by suppressing ICAM-1 expression in HUVECs.

Advanced Glycation End Products Induce Atherosclerosis via RAGE/TLR4 Signaling Mediated-M1 Macrophage Polarization-Dependent Vascular Smooth Muscle Cell Phenotypic Conversion

“…Inhibition of ERK effectively suppressed plaque formation and vascular remodeling in atherosclerotic mice [ 11 ]. FOXC2 overexpression promoted atherosclerosis by facilitating cell adhesion capability [ 12 ]. Thus, it is reasonable for us to hypothesize that AGEs endow macrophages with Dll4 high expression during M0 to M1 polarization.…”

Defects in vein valve PROX1/FOXC2 antithrombotic pathway in endothelial cells drive the hypercoagulable state induced by trauma and critical illness

“…This does not, however, rule out a FOXC2-dependent pathway, as, in addition to OSS, FOXC2 is downstream of multiple inflammatory mediators. One established example is of lipopolysaccharaide signaling through TLR4 results in ERK2-mediated phosphorylation of FOXC2, which shifts gene expression toward angiogenesis in human primary pulmonary microvascular endothelial cells 37 and downregulation of new FOXC2 transcription 38 . Finally, with regard to kinetics, we only look at acute changes in the murine model at 24 hours, and there is more information to be gleaned about the persistence, durability, and timeline of this effect in this model of injury.…”

“…One established example is of lipopolysaccharaide signaling through TLR4 results in ERK2-mediated phosphorylation of FOXC2, which shifts gene expression toward angiogenesis in human primary pulmonary microvascular endothelial cells 37 and downregulation of new FOXC2 transcription. 38 Finally, with regard to kinetics, we only look at acute changes in the murine model at 24 hours, and there is more information to be gleaned about the persistence, durability, and timeline of this effect in this model of injury. Data from additional time points may identify the kinetics of the effect, which may provide additional insight into the molecular genetics behind the change in valve phenotype in trauma.…”

Synergistic Effect of Polydatin and Polygonatum sibiricum Polysaccharides in Combating Atherosclerosis via Suppressing TLR4-Mediated NF-κB Activation in ApoE-Deficient Mice

“…Endothelial dysfunction is identified as an early indicator of atherosclerosis and is characterized by the high expression of VCAM-1 and ICAM-1 [ 40 ]. Previous studies have confirmed that ICAM-1 plays a vital role in the pathogenesis of atherosclerosis and the influences of many risk factors may be also mediated through their effects on ICAM-1 [ 41 ]. It was verified that PSP could increase liver antioxidant enzyme activities.…”