Modulation of endothelial cell proliferation and capillary network formation by the ox-LDL component: 1-palmitoyl-2-archidonoyl-sn-glycero-3-phosphocholine (ox-PAPC)

Abstract

Atherosclerotic plaque formation is often associated with pathological angiogenesis. Modified phospholipids, including oxidized lipoproteins such as LDL, are found to induce adhesion of the monocytes to the endothelial cells and to stimulate their chemotaxis. Effects of oxidized 1-palmitoyl-2-archidonoyl-sn-glycero-3-phosphocholine (ox-PAPC) mimic actions of minimally modified LDL in vivo. Interleukin-8 (IL-8) and interleukin-15 (IL-15) are known to induce both inflammation and angiogenesis. The goal of our study was to analyze a potential synergism between ox-PAPC and IL-15 in the in vitro model of angiogenesis carried out in the human endothelial cells (HUVECs). Increasing IL-15 concentrations led to formation of the tube-like structures in the matrigel 3D-model of angiogenesis (P \ 0.05), in contrast to ox-PAPC that inhibited this process. HUVECs incubation with ox-PAPC led to reduced IL-15 gene basal expression (P = 0.033) along with parallel increase, however statistically insignificant, of basal gene expression of IL-8 (P = 0.086). Our findings point to the ox-PAPC opposite effects on the IL-8-and IL-15-mediated angiogenic responses that contribute to pathological angiogenesis induced by ox-LDL.

4-Hydroxynonenal Contributes to Angiogenesis through a Redox-Dependent Sphingolipid Pathway: Prevention by Hydralazine Derivatives

“…These compounds exhibit a potent antiatherogenic effect in the apoE−/− murine model of atherosclerosis [30, 39]. We report here that both Hdz and BVH prevent the angiogenic effect of 4-HNE.…”

“…Another aim of this study was to investigate the antiangiogenic properties of hydralazine (Hdz), an antihypertensive drug with carbonyl scavenger activity, and of its derivative bisvanillyl-hydralazone (BVH), in which hydralazine is covalently bound to bisvanillin, a phenolic antioxidant. These compounds exhibit a potent antiatherogenic effect in the apoE−/− murine model of atherosclerosis [ 30 , 39 ]. We report here that both Hdz and BVH prevent the angiogenic effect of 4-HNE.…”

“…We report here that both Hdz and BVH prevent the angiogenic effect of 4-HNE. Hdz is a potent carbonyl scavenger that reacts rapidly with 4-HNE and prevents the formation of 4-HNE-protein adducts [ 30 ]. BVH, which is constituted by two molecules of Hdz associated with the antioxidant BV, is able to scavenge 4-HNE and block intracellular ROS generated by cells [ 39 ].…”

“…Oxidized phospholipids exhibit proinflammatory [ 28 ] and proangiogenic properties [ 29 ]. Oxidation derivatives of arachidonic acid may act as initiators of atherogenesis and trigger endothelial cell proliferation and capillary network formation [ 30 ]. Oxidized LDLs (oxLDLs) exhibit a dual dose-dependent angiogenic effect, since low oxLDL concentrations are angiogenic, while higher concentrations are not angiogenic and are rather cytotoxic [ 31 – 35 ].…”