Journal article
CD14 Directs Adventitial Macrophage Precursor Recruitment: Role in Early Abdominal Aortic Aneurysm Formation
Journal of the American Heart Association, Vol.2(2), pp.e000065-e000065
03/12/2013
DOI: 10.1161/JAHA.112.000065
PMCID: PMC3647288
PMID: 23537804
Abstract
Background
Recruitment of macrophage precursors to the adventitia plays a key role in the pathogenesis of abdominal aortic aneurysms (AAAs), but molecular mechanisms remain undefined. The innate immune signaling molecule CD14 was reported to be upregulated in adventitial macrophages in a murine model of AAA and in monocytes cocultured with aortic adventitial fibroblasts (AoAf) in vitro, concurrent with increased interleukin‐6 (IL‐6) expression. We hypothesized that CD14 plays a crucial role in adventitial macrophage precursor recruitment early during AAA formation.
Methods and Results
CD14−/− mice were resistant to AAA formation induced by 2 different AAA induction models: aortic elastase infusion and systemic angiotensin II (AngII) infusion. CD14 gene deletion led to reduced aortic macrophage infiltration and diminished elastin degradation. Adventitial monocyte binding to AngII‐infused aorta in vitro was dependent on CD14, and incubation of human acute monocytic leukemia cell line‐1 (THP‐1) monocytes with IL‐6 or conditioned medium from perivascular adipose tissue (PVAT) upregulated CD14 expression. Conditioned medium from AoAf and PVAT induced CD14‐dependent monocyte chemotaxis, which was potentiated by IL‐6. CD14 expression in aorta and plasma CD14 levels were increased in AAA patients compared with controls.
Conclusions
These findings link CD14 innate immune signaling via a novel IL‐6 amplification loop to adventitial macrophage precursor recruitment in the pathogenesis of AAA.
Details
- Title: Subtitle
- CD14 Directs Adventitial Macrophage Precursor Recruitment: Role in Early Abdominal Aortic Aneurysm Formation
- Creators
- Andra L Blomkalns - Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, OHDaniel Gavrila - Division of Cardiovascular Medicine, University of Iowa, Iowa City, IowaManesh Thomas - Division of Cardiovascular Medicine, University of Iowa, Iowa City, IowaBonnie S Neltner - Division of Cardiovascular Diseases, University of Cincinnati College of Medicine, Cincinnati, OHVictor M Blanco - Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, OHStephanie B Benjamin - Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, OHMichael L McCormick - Department of Radiation Oncology, University of Iowa, Iowa City, IowaLynn L Stoll - Department of Emergency Medicine, University of Iowa, Iowa City, IowaGerene M Denning - Department of Emergency Medicine, University of Iowa, Iowa City, IowaSean P Collins - Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, OHZhenyu Qin - Division of Cardiovascular Diseases, University of Cincinnati College of Medicine, Cincinnati, OHAlan Daugherty - University of Kentucky, Lexington, KentuckyLisa A Cassis - Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KentuckyRobert W Thompson - Department of Surgery (Section of Vascular Surgery), Washington University School of Medicine, St. Louis, MissouriRobert M Weiss - Division of Cardiovascular Medicine, University of Iowa, Iowa City, IowaPaul D Lindower - Division of Cardiovascular Medicine, University of Iowa, Iowa City, IowaSusan M Pinney - Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OHTapan Chatterjee - Division of Cardiovascular Diseases, University of Cincinnati College of Medicine, Cincinnati, OHNeal L Weintraub - Division of Cardiovascular Diseases, University of Cincinnati College of Medicine, Cincinnati, OH
- Resource Type
- Journal article
- Publication Details
- Journal of the American Heart Association, Vol.2(2), pp.e000065-e000065
- DOI
- 10.1161/JAHA.112.000065
- PMID
- 23537804
- PMCID
- PMC3647288
- ISSN
- 2047-9980
- eISSN
- 2047-9980
- Language
- English
- Date published
- 03/12/2013
- Academic Unit
- Radiology; Emergency Medicine; Cardiovascular Medicine; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984094397802771
Metrics
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