Interferon-γ and the Interferon-Inducible Chemokine CXCL10 Protect Against Aneurysm Formation and Rupture
- 27 January 2009
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 119 (3), 426-435
- https://doi.org/10.1161/circulationaha.108.785949
Abstract
Background—Vascular disease can manifest as stenotic plaques or ectatic aneurysms, although the mechanisms culminating in these divergent disease manifestations remain poorly understood. T-helper type 1 cytokines, including interferon-γ and CXCL10, have been strongly implicated in atherosclerotic plaque development.Methods and Results—Here, we specifically examined their role in the formation of abdominal aortic aneurysms in the angiotensin II–induced murine model. Unexpectedly, we found increased suprarenal aortic diameters, abdominal aortic aneurysm incidence, and aneurysmal death in apolipoprotein E– and interferon-γ–deficient (Apoe−/−/Ifng−/−) mice compared withApoe−/−controls, although atherosclerotic luminal plaque formation was attenuated. The interferon-γ–inducible T-cell chemoattractant CXCL10 was highly induced by angiotensin II infusion inApoe−/−mice, but this induction was markedly attenuated inApoe−/−/Ifng−/−mice.Apoe−/−/Cxcl10−/−mice had decreased luminal plaque but also increased aortic size, worse morphological grades of aneurysms, and a higher incidence of death due to aortic rupture than Apoe−/−controls. Furthermore, abdominal aortic aneurysms inApoe−/−/Cxcl10−/−mice were enriched for non–T-helper type 1–related signals, including transforming growth factor-β1. Treatment ofApoe−/−/Cxcl10−/−mice with anti-transforming growth factor-β neutralizing antibody diminished angiotensin II–induced aortic dilation.Conclusions—The present study defines a novel pathway in which interferon-γ and its effector, CXCL10, contribute to divergent pathways in abdominal aortic aneurysm versus plaque formation, inhibiting the former pathology but promoting the latter. Thus, efforts to develop antiinflammatory strategies for atherosclerosis must carefully consider potential effects on all manifestations of vascular disease.This publication has 48 references indexed in Scilit:
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