Regulatory T cells in human and angiotensin II-induced mouse abdominal aortic aneurysms.

Abstract

AIMS:

Regulatory T cells (Tregs) protect mice from angiotensin II (Ang-II)-induced abdominal aortic aneurysms (AAA). This study tested whether AAA patients are Treg-insufficient and the Treg molecular mechanisms that control AAA pathogenesis.

METHODS AND RESULTS:

ELISA determined the Foxp3 concentration in blood cell lysates from 485 AAA patients and 204 age- and sex-matched controls. AAA patients exhibited lower blood cell Foxp3 expression than controls (P < 0.0001). Pearson's correlation test demonstrated a significant but negative correlation between Foxp3 and AAA annual expansion rate before (r = -0.147, P = 0.007) and after (r = -0.153, P = 0.006) adjustment for AAA risk factors. AAA in apolipoprotein E-deficient (Apoe(-/-)) mice that received different doses of Ang-II exhibited a negative correlation of lesion Foxp3(+) Treg numbers with AAA size (r = -0.883, P < 0.0001). Adoptive transfer of Tregs from wild-type (WT) and IL10-deficient (Il10(-/-)) mice increased AAA lesion Treg content, but only WT mice Tregs reduced AAA size, AAA incidence, blood pressure, lesion macrophage and CD4(+) and CD8(+) T-cell accumulation, and angiogenesis with concurrent increase of lesion collagen content. Both AAA lesion immunostaining and plasma ELISA demonstrated that adoptive transfer of WT Tregs, but not Il10(-/-) Tregs, reduced the expression of MCP-1. In vitro cell culture and aortic ring assay demonstrated that only Tregs from WT mice, but not those from Il10(-/-) mice, reduced macrophage MCP-1 secretion, macrophage and vascular cell protease expression and activity, and aortic ring microvessel formation.

CONCLUSION:

This study supports a protective role of Tregs in human and experimental AAA by releasing IL10 to suppress inflammatory cell chemotaxis, arterial wall remodelling, and angiogenesis.

• Authors: Yi Zhou, Wenxue Wu, Jes S Lindholt, Galina K Sukhova, Peter Libby, Xueqing Yu, Guo-Ping Shi
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 107 Issue 1 Pg. 98-107 (Jul 01 2015) ISSN: 1755-3245 [Electronic] England
• PMID: 25824145 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: [email protected].

Chemical References

• Chemokines
• FOXP3 protein, human
• Forkhead Transcription Factors
• Angiotensin II
• Interleukin-10

Topics

• Aged
• Angiotensin II (pharmacology)
• Animals
• Aortic Aneurysm, Abdominal (etiology, prevention & control)
• Chemokines (biosynthesis)
• Forkhead Transcription Factors (analysis)
• Humans
• Interleukin-10 (physiology)
• Male
• Mice
• Mice, Inbred C57BL
• Neovascularization, Physiologic
• T-Lymphocytes, Regulatory (physiology)