Vascular endothelial growth factor synergistically enhances induction of E-selectin by tumor necrosis factor-alpha.

Objective: The regulation of endothelial cell adhesion molecules (CAMs) by vascular endothelial growth factor (VEGF) was investigated in cell cultures and in a rabbit model of atherogenic neointima formation.

Methods And Results: VEGF regulation of vascular CAM-1 (vascular cell adhesion molecule), intercellular CAM-1 (intercellular adhesion molecule), and E-selectin were investigated in human umbilical vein endothelial cells using quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and flow cytometry, and in the rabbit collar model of atherogenic macrophage accumulation by immunostaining. VEGF alone caused no significant induction of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, or E-selectin compared with tumor necrosis factor-alpha.

Apolipoprotein E (apoE) isoforms differentially induce nitric oxide production in endothelial cells.

Although apolipoprotein E3 (apoE3) is atheroprotective, two common isoforms, apoE2 and apoE4, produce recessive and dominant hyperlipidaemias, respectively. Using a fluorescent assay, we report herein that apoE3 particles secreted from recombinant cells stimulate more nitric oxide release in cultured human EA.hy926 endothelial cells than apoE2 or apoE4 (141% more than controls vs.

Acute regression of advanced and retardation of early aortic atheroma in immunocompetent apolipoprotein-E (apoE) deficient mice by administration of a second generation [E1(-), E3(-), polymerase(-)] adenovirus vector expressing human apoE.

Apolipoprotein E (apoE) is a 34 kDa glycoprotein with multiple actions that help protect against the development of atherosclerosis. Here, we have assessed the atheroprotective potential of an [E1(-), E3(-), polymerase(-)] adenovirus vector expressing human apoE, comparing intramuscular and intravenous (liver-directed) injections in hypercholesterolaemic apoE-deficient mice (apoE(-/-)). Intramuscular injections resulted in low expression of apoE and afforded no protection against atherogenesis.