Elastin-derived peptides promote abdominal aortic aneurysm formation by modulating m1/m2 macrophage polarization

Matthew A. Dale, Wanfen Xiong, Jeffrey S. Carson, Melissa K. Suh, Andrew D. Karpisek, Trevor M. Meisinger, George P Casale, Bernard Timothy Baxter

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Abdominal aortic aneurysm is a dynamic vascular disease characterized by inflammatory cell invasion and extracellular matrix degradation. Damage to elastin in the extracellular matrix results in release of elastin-derived peptides (EDPs), which are chemotactic for inflammatory cells such as monocytes. Their effect on macrophage polarization is less well known. Proinflammatory M1 macrophages initially are recruited to sites of injury, but, if their effects are prolonged, they can lead to chronic inflammation that prevents normal tissue repair. Conversely, anti-inflammatory M2 macrophages reduce inflammation and aid in wound healing. Thus, a proper M1/M2 ratio is vital for tissue homeostasis. Abdominal aortic aneurysm tissue reveals a high M1/M2 ratio in which proinflammatory cells and their associated markers dominate. In the current study, in vitro treatment of bone marrow-derived macrophages with EDPs induced M1 macrophage polarization. By using C57BL/6 mice, Ab-mediated neutralization of EDPs reduced aortic dilation, matrix metalloproteinase activity, and proinflammatory cytokine expression at early and late time points after aneurysm induction. Furthermore, direct manipulation of the M1/M2 balance altered aortic dilation. Injection of M2-polarized macrophages reduced aortic dilation after aneurysm induction. EDPs promoted a proinflammatory environment in aortic tissue by inducing M1 polarization, and neutralization of EDPs attenuated aortic dilation. The M1/M2 imbalance is vital to aneurysm formation.

Original languageEnglish (US)
Pages (from-to)4536-4543
Number of pages8
JournalJournal of Immunology
Volume196
Issue number11
DOIs
StatePublished - Jun 1 2016

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Elastin
Abdominal Aortic Aneurysm
Macrophages
Peptides
Dilatation
Aneurysm
Extracellular Matrix
Inflammation
Matrix Metalloproteinases
Inbred C57BL Mouse
Vascular Diseases
Wound Healing
Monocytes
Homeostasis
Anti-Inflammatory Agents
Cytokines
Injections
Wounds and Injuries

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Elastin-derived peptides promote abdominal aortic aneurysm formation by modulating m1/m2 macrophage polarization. / Dale, Matthew A.; Xiong, Wanfen; Carson, Jeffrey S.; Suh, Melissa K.; Karpisek, Andrew D.; Meisinger, Trevor M.; Casale, George P; Baxter, Bernard Timothy.

In: Journal of Immunology, Vol. 196, No. 11, 01.06.2016, p. 4536-4543.

Research output: Contribution to journalArticle

Dale, Matthew A. ; Xiong, Wanfen ; Carson, Jeffrey S. ; Suh, Melissa K. ; Karpisek, Andrew D. ; Meisinger, Trevor M. ; Casale, George P ; Baxter, Bernard Timothy. / Elastin-derived peptides promote abdominal aortic aneurysm formation by modulating m1/m2 macrophage polarization. In: Journal of Immunology. 2016 ; Vol. 196, No. 11. pp. 4536-4543.
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