Abstract 2059: Apelin Potently Inhibits Angiotensin and Disease Induced Superoxide Generation and Associated Vascular Remodeling in Vein Grafts
Signaling through the apelin-APJ pathway may have a significant role in cardiovascular physiology and disease. Evidence suggests that these actions are mediated in part through regulation of angiotensin (AngII) pathways, which have been implicated in the development of vein graft (VG) neointimal hyperplasia (NIH) after bypass surgery. To investigate the hypothesis that apelin could attenuate vascular remodeling through antagonism of AngII pathways, we constructed VGs in four groups of ApoE-KO mice implanted with osmotic minipumps: apelin, saline, AngII or AngII + apelin. Continuous infusion pumps were implanted one day pre-operatively and remained in place until grafts were harvested 28 days post surgery (n=20). Apelin significantly reduced NIH and vessel wall area compared to saline treated controls. Infusion of AngII induced an increase in vessel wall area predominantly outside the neointima. Addition of apelin rescued this outward remodeling, reducing total vessel wall area compared to AngII treated mice to saline treated control levels. Since reactive oxygen species are thought to be the predominant mechanism by which AngII promotes vein graft NIH and vascular remodeling, we assessed O2− production, via lucigenin luminescence and dihydroethidium fluorescence. O2− production was significantly attenuated in aortas of apelin treated mice compared to saline control and apelin + AngII treated mice compared to AngII. Furthermore, O2− levels in apelin + AngII treated mice were significantly reduced compared to saline controls. Morphometric analysis of vascular sections revealed that apelin inhibited O2− production from endothelium but much more markedly from medial SMCs. In summary, apelin reduces NIH and vascular remodeling in ApoE-KO mice under basal and AngII stimulated conditions in association with a reduction in O2− production from predominantly medial SMCs. This study highlights the importance of the apelin/APJ pathway in vascular remodeling.