Foxp3+ Regulatory T Cells Play a Protective Role in Angiotensin II–Induced Aortic Aneurysm Formation in Mice. Issue 4 (April 2015)

• Record Type: Journal Article
• Authors: Yodoi, Keiko; Yamashita, Tomoya; Sasaki, Naoto; Kasahara, Kazuyuki; Emoto, Takuo; Matsumoto, Takuya; Kita, Tomoyuki; Sasaki, Yoshihiro; Mizoguchi, Taiji; Sparwasser, Tim; Hirata, Ken-ichi
• Is Part Of: Hypertension. Volume 65:Issue 4(2015:Apr.)
• Publication Date: 2015-04
• Subjects: aortic aneurysm, abdominal -- immunology -- inflammation -- interleukin-2 -- T-lymphocytes, regulatory; Hypertension -- Periodicals; Hypertension -- Treatment -- Periodicals; 616.132005
• DOI: 10.1161/HYPERTENSIONAHA.114.04934
• Languages: English
• ISSNs: 0194-911X

Abstract

Abstract : Although regulatory T cells (Tregs) have been shown to play a protective role in abdominal aortic aneurysm (AAA) formation, it remains unclear whether expansion of endogenous Foxp3 + Tregs prevents AAA. In the current study, we determined the effects of endogenous Foxp3 + Treg expansion or depletion in an experimental model of AAA. We continuously infused 12-week-old apolipoprotein E–deficient mice fed a high-cholesterol diet with angiotensin II (n=60) or normal saline (n=12) by implanting osmotic mini-pumps and evaluated AAA formation at 16 weeks. The angiotensin II–infused mice received interleukin-2/anti–interleukin-2 monoclonal antibody complex (interleukin-2 complex; n=31) or PBS (n=29). Eighty-one percent of angiotensin II–infused mice developed AAA, with 42% mortality possibly because of aneurysm rupture. Interleukin-2 complex treatment systemically increased the number of Foxp3 + Tregs and significantly decreased the incidence (52%) and mortality (17%) of AAA. Immunohistochemical analysis showed reduced accumulation of macrophages and increased numbers of Foxp3 + Tregs in aneurysmal tissues, suggesting that expansion of Tregs may suppress local inflammation in the vessel wall and provide protection against AAA formation. Furthermore, genetic depletion of Foxp3 + Tregs led to a significant increase in the mortality of AAA, suggesting the protective role of Foxp3 + Tregs against AAA. Our findings suggest that Foxp3 + Tregs may play a protective role in AAA formation and that promotion of an endogenous regulatory immune response may be a potentially valuable therapeutic approach for preventing AAA. Abstract : Supplemental Digital Content is available in the text.