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This Article Full Text Full Text (PDF) All Versions of this Article: 296/5/H1329    most recent 01341.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Leeper, N. J. Articles by Quertermous, T. Search for Related Content PubMed PubMed Citation Articles by Leeper, N. J. Articles by Quertermous, T.

Apelin prevents aortic aneurysm formation by inhibiting macrophage inflammation

¹Division of Cardiovascular Medicine, Department of Medicine and ²Division of Vascular Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California

Submitted 30 December 2008 ; accepted in final form 16 March 2009

Apelin is a potent inodilator with recently described antiatherogenic properties. We hypothesized that apelin might also attenuate abdominal aortic aneurysm (AAA) formation by limiting disease-related vascular wall inflammation. C57BL/6 mice implanted with osmotic pumps filled with apelin or saline were treated with pancreatic elastase to create infrarenal AAAs. Mice were euthanized for aortic PCR analysis or followed ultrasonographically and then euthanized for histological analysis. The cellular expression of inflammatory cytokines and chemokines in response to apelin was also assessed in cultured macrophages, smooth muscle cells, and fibroblasts. Apelin treatment resulted in diminished AAA formation, with a 47% reduction in maximal cross-sectional area (0.74 vs. 1.39 mm², P < 0.03) and a 57% reduction in macrophage infiltrate (113 vs. 261.3 cells/high-power field, P < 0.0001) relative to the saline-treated group. Apelin infusion was also associated with significantly reduced aortic macrophage colony-stimulating factor expression and decreased monocyte chemattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1, interleukin (IL)-6, and tumor necrosis factor (TNF)- mean mRNA levels. Apelin stimulation of cultured macrophages significantly reduced MCP-1 and TNF- mRNA levels relative to baseline (2.03- and 1.89-fold reduction, P < 0.03, respectively) but did not affect intimal adhesion molecule expression or medial or adventitial cell cytokine production. Apelin significantly reduces aneurysm formation in the elastase model of human AAA disease. The mechanism appears to be decreased macrophage burden, perhaps related to an apelin-mediated decrease in proinflammatory cytokine and chemokine activation.

abdominal aortic aneurysms; vascular disease; chemokine; inflammatory cytokine