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)
|