Abstract 18756: Apelin is Crucial for the (Pro-Inflammatory) Activation of Endothelial Cells in Advanced Plaque Progression
Recent findings have linked activation of endothelial cells (ECs) into a more pro-inflammatory phenotype with new vessel growth in atherosclerotic plaques, and plaque destabilization. Apelin signaling is a potent vascular regulatory pathway that mainly functions through ECs. Apelin levels are increased in human atherosclerotic lesions, but the effect of apelin on advanced atherosclerotic lesions remains unknown.
Apelin infusion in ApoE KO mice with advanced lesionsresulted in enhanced plaque vulnerability without altering the lesion size (P<0.01, n=10). Apelin proved to increase plaque neovascularization and hemorrhaging (P<0.05, n=10). In addition, apelin infusion resulted in endothelial expression of adhesion factors and cytokines, e.g. VCAM-1 and MCP1 (P<0.05, n=10).
In line, in vitro analysis demonstrated that apelin acts synergistically with the pro-inflammatory cytokine, TNFα, in enhancing the endothelial expression of adhesion factors and cytokines, including VCAM-1 and MCP1 (P<0.05, n=6) and loss of the endothelial barrier function (P<0.05, n=6). In addition, apelin activates eNOS by phosphorylation and may thereby aggravating the pro-inflammatory state of the ECs, by ROS generation. For, apelin enhanced phosphorylated eNOS in cultured ECs under all conditions (P<0.05, n=6), whereas ROS production was only augmented by apelin when combined with TNFα (P<0.05, n=6).
We provide for the first time, evidence for the role of apelin in advanced plaque destabilization by promoting growth of the intraplaque vasculature and by activation of endothelial cells into a disease-prone phenotype.
- © 2013 by American Heart Association, Inc.