Small Concentrations of oxLDL Induce Capillary Tube Formation From Endothelial Cells via LOX-1–Dependent Redox-Sensitive Pathway

Abstract

Objective-Vascular endothelial growth factor (VEGF), a key angiogenic growth factor, stimulates angiogenesis. Low levels of reactive oxygen species (ROS) function as signaling molecules for angiogenesis. We postulated that low concentrations of oxLDL might induce low levels of ROS and initiate angiogenesis. Methods and Results-An in vitro model of tube formation from human coronary artery endothelial cells (HCAECs) was used.oxLDL (0.1, 1, 2, 5 g/mL) induced VEGF expression and enhanced tube formation. oxLDL-mediated VEGF expression and tube formation were suppressed by a specific blocking anti-LOX-1 antibody. Anti-LOX-1 antibody also reduced oxLDL-induced increase in the expression of NADPH oxidase (gp91 phox and p47 phox subunits) and subsequent intracellular ROS generation, phosphorylation of p38 as well as p44/42MAPK, and NF-B p65 expression. gp91 phox siRNA had a similar effect. The expression of VEGF and NF-B p65 induced by oxLDL was also inhibited by the specific extracellular signal-regulated kinase (ERK) 1/2 inhibitor U0126 and the p38 MAPK inhibitor SB203580. Importantly, the NADPH oxidase inhibitor apocynin, gp91 phox siRNA, U0126, and SB203580 all reduced tube formation in response to oxLDL. Conclusions-These

Oxidized LDL signals through Rho-GTPase to induce endothelial cell stiffening and promote capillary formation

“…Our studies, however, showed that oxLDL may have a positive effect on the formation of endothelial networks in a 3D in vitro model of angiogenesis (3,18). Consistent with these findings, a similar effect was shown in a 2D system (19). Most recently, it was shown that oxLDL also has a pro-angiogenic effect in vivo (20,21), possibly in a macrophage-dependent way (20).…”

Ovulation as danger signaling event of innate immunity

“…Cell death ensues (Mehta et al, 2006;Chen et al, 2007). The amount of ROS determines beneficial or detrimental effects, either for endothelial cell survival or apoptosis (Dandapat et al, 2007). The same could hold true for the preovulatory follicle.…”

Indoxyl Sulfate Stimulates Monocyte Chemoattractant Protein-1 Expression in Human Umbilical Vein Endothelial Cells by Inducing Oxidative Stress Through Activation of the NADPH Oxidase-Nuclear Factor-.KAPPA.B Pathway

“…21 According to recent studies, ROS derived from NADPH oxidase is involved in the regulation of MCP-1 gene expression in endothelial cells. 19, 22 The aim of this study was to determine if IS induced ROS production by activating NADPH oxidase, leading to the induction of MCP-1 expression in human umbilical vein endothelial cells (HUVEC), and to clarify the mechanisms involved.…”

“…As several reports have shown that ROS induces MCP-1 expression in endothelial cells, 19,22 and that NADPH oxidase is a major source of superoxide in vascular cells and monocytes, 25 we examined the effect of apocynin (600 μmol/L), a specific NADPH oxidase inhibitor, on IS-induced ROS production and MCP-1 expression. As shown in Figure 2A, HUVEC treated with IS for 2 min exhibited increased superoxide production compared with the controls, but pretreatment with apocynin for 30 min significantly reduced their ROS production, indicating that IS-induced ROS production in HUVEC was most likely derived from NADPH oxidase activity.…”

“…According to a recent study, some oxidants, including oxLDL, activate NF-κB via MAPK. 22 Therefore, we examined whether inhibitors of ERK1/2 and p38 affected NF-κB activation by IS. As expected, the combination of PD98059 and SB203580 blocked IS-induced translocation of p65 into the nucleus (Figure 5B).…”