Deficiency of ITGAM Attenuates Experimental Abdominal Aortic Aneurysm in Mice

Background Integrin αM (CD11b), which is encoded by the Integrin Subunit Alpha M (ITGAM) gene, is not only a surface marker of monocytes but also an essential adhesion molecule. In this study, we investigated the effect of CD11b on experimental abdominal aortic aneurysm and the potential underlying mechanisms. Methods and Results The incidence of abdominal aortic aneurysm was not significantly lower in ITGAM(‐/‐) mice than in control mice. Nevertheless, knockout of CD11b reduced the maximum abdominal aortic diameter, macrophage infiltration, matrix metalloproteinase‐9 expression, and elastin and collagen degradation. Additionally, lower expression of IL‐6 was found in both the peripheral blood and abdominal aortas of ITGAM(‐/‐) mice, indicating a biological correlation between CD11b and the inflammatory response in abdominal aortic aneurysm. In vitro, the number of ITGAM(‐/‐) bone marrow–derived macrophages (BMDMs) that adhered to endothelial cells was significantly lower than the number of wild‐type BMDMs. Moreover, the CD11b monoclonal antibody and CD11b agonist leukadherin‐1 decreased and increased the number of adherent wild‐type BMDMs, respectively. Through RNA sequencing, genes associated with leukocyte transendothelial migration were found to be downregulated in ITGAM(‐/‐) BMDMs. Furthermore, immunoprecipitation–mass spectrometry analysis predicted that the Akt pathway might be responsible for the impaired transmigratory ability of ITGAM(‐/‐) BMDMs. The reduced activation of Akt was then confirmed, and the Akt agonist SC79 partially rescued the transendothelial migratory function of ITGAM(‐/‐) BMDMs. Conclusions CD11b might promote the development and progression of abdominal aortic aneurysm by mediating the endothelial cells adhesion and transendothelial migration of circulating monocytes/macrophages.

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Quantitative Mass Spectrometry Analysis Using PAcIFIC for the Identification of Plasma Diagnostic Biomarkers for Abdominal Aortic Aneurysm

PLoS ONE ◽

10.1371/journal.pone.0028698 ◽

2011 ◽

Vol 6 (12) ◽

pp. e28698 ◽

Cited By ~ 26

Author(s):

Adelina E. Acosta-Martin ◽

Alexandre Panchaud ◽

Maggy Chwastyniak ◽

Annabelle Dupont ◽

Francis Juthier ◽

...

Keyword(s):

Mass Spectrometry ◽

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Mass Spectrometry Analysis ◽

Plasma Diagnostic ◽

Quantitative Mass Spectrometry ◽

Diagnostic Biomarkers ◽

Spectrometry Analysis ◽

Abdominal Aortic

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Identification of Novel Long Noncoding RNAs and Their Role in Abdominal Aortic Aneurysm

BioMed Research International ◽

10.1155/2020/3502518 ◽

2020 ◽

Vol 2020 ◽

pp. 1-22

Author(s):

Abulaihaiti Maitiseyiti ◽

Hongbo Ci ◽

Qingbo Fang ◽

Sheng Guan ◽

Alimujiang Shawuti ◽

...

Keyword(s):

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Expression Profiles ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Functional Enrichment ◽

Pcr Analysis ◽

Control Group ◽

Abdominal Aortic

Objective. Long noncoding RNAs (lncRNAs) have emerged as critical molecular regulators in various diseases. However, the potential regulatory role of lncRNAs in the pathogenesis of abdominal aortic aneurysm (AAA) remains elusive. The aim of this study was to identify crucial lncRNAs associated with human AAA by comparing the lncRNA and mRNA expression profiles of patients with AAA with those of control individuals. Materials and Methods. The expression profiles of lncRNAs and mRNAs were analyzed in five dilated aortic samples from AAA patients and three normal aortic samples from control individuals using microarray technology. Functional annotation of the screened lncRNAs based on the differentially expressed genes was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results. Microarray results revealed 2046 lncRNAs and 1363 mRNAs. Functional enrichment analysis showed that the mRNAs significantly associated with AAA were enriched in the NOD-like receptor (NLR) and nuclear factor kappa-B (NF-κB) signaling pathways and in cell adhesion molecules (CAMs), which are closely associated with pathophysiological changes in AAA. The lncRNAs identified using microarray analysis were further validated using quantitative real-time polymerase chain reaction (qRT-PCR) analysis with 12 versus 11 aortic samples. Finally, three key lncRNAs (ENST00000566954, ENST00000580897, and T181556) were confirmed using strict validation. A coding-noncoding coexpression (CNC) network and a competing endogenous RNA (ceRNA) network were constructed to determine the interaction among the lncRNAs, microRNAs, and mRNAs based on the confirmed lncRNAs. Conclusions. Our microarray profiling analysis and validation of significantly expressed lncRNAs between patients with AAA and control group individuals may provide new diagnostic biomarkers for AAA. The underlying regulatory mechanisms of the confirmed lncRNAs in AAA pathogenesis need to be determined using in vitro and in vivo experiments.

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A Novel In Vitro Method for Assessing the Resistance to Distal Displacement of Endovascular Stent Grafts for Abdominal Aortic Aneurysm Repair

IFMBE Proceedings - World Congress on Medical Physics and Biomedical Engineering, September 7 - 12, 2009, Munich, Germany ◽

10.1007/978-3-642-03906-5_66 ◽

2009 ◽

pp. 243-246

Author(s):

T. J. Corbett ◽

A. Callanan ◽

M. R. O’Donnell ◽

T. M. McGloughlin

Keyword(s):

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Abdominal Aortic Aneurysm Repair ◽

Endovascular Stent ◽

Stent Grafts ◽

In Vitro Method ◽

Abdominal Aortic ◽

Aneurysm Repair ◽

Aortic Aneurysm Repair

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Genetic and Epigenetic Mechanisms Underlying Vascular Smooth Muscle Cell Phenotypic Modulation in Abdominal Aortic Aneurysm

International Journal of Molecular Sciences ◽

10.3390/ijms21176334 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6334

Author(s):

Rijan Gurung ◽

Andrew Mark Choong ◽

Chin Cheng Woo ◽

Roger Foo ◽

Vitaly Sorokin

Keyword(s):

Smooth Muscle ◽

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Smooth Muscle Cells ◽

Aortic Wall ◽

Epigenetic Mechanisms ◽

Phenotypic Modulation ◽

Abdominal Aortic

Abdominal aortic aneurysm (AAA) refers to the localized dilatation of the infra-renal aorta, in which the diameter exceeds 3.0 cm. Loss of vascular smooth muscle cells, degradation of the extracellular matrix (ECM), vascular inflammation, and oxidative stress are hallmarks of AAA pathogenesis and contribute to the progressive thinning of the media and adventitia of the aortic wall. With increasing AAA diameter, and left untreated, aortic rupture ensues with high mortality. Collective evidence of recent genetic and epigenetic studies has shown that phenotypic modulation of smooth muscle cells (SMCs) towards dedifferentiation and proliferative state, which associate with the ECM remodeling of the vascular wall and accompanied with increased cell senescence and inflammation, is seen in in vitro and in vivo models of the disease. This review critically analyses existing publications on the genetic and epigenetic mechanisms implicated in the complex role of SMCs within the aortic wall in AAA formation and reflects the importance of SMCs plasticity in AAA formation. Although evidence from the wide variety of mouse models is convincing, how this knowledge is applied to human biology needs to be addressed urgently leveraging modern in vitro and in vivo experimental technology.

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Development of fibrinous thrombus analogue for in-vitro abdominal aortic aneurysm studies

Journal of Biomechanics ◽

10.1016/j.jbiomech.2006.01.010 ◽

2007 ◽

Vol 40 (2) ◽

pp. 289-295 ◽

Cited By ~ 21

Author(s):

J.W. Hinnen ◽

D.J. Rixen ◽

O.H.J. Koning ◽

J.H. van Bockel ◽

J.F. Hamming

Keyword(s):

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Abdominal Aortic

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The Development of Physiological Compliant Abdominal Aortic Aneurysm Models for In Vitro Flow Studies

ASME 2009 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2009-206608 ◽

2009 ◽

Author(s):

Timothy J. Corbett ◽

Barry J. Doyle ◽

Anthony Callanan ◽

Tim M. McGloughlin

Keyword(s):

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Material Properties ◽

Abdominal Aortic Aneurysms ◽

Aortic Aneurysms ◽

Flow Loop ◽

The Past ◽

Abdominal Aortic

A vast amount of experimental research has been undertaken in the past decade to investigate different aspects of preoperative and postoperative abdominal aortic aneurysms (AAAs). Much of this research has been based on the use of mock arteries in an in vitro flow loop to mimic the behaviour of the abdominal aorta in vivo [1]. These models should be reproducible, have consistent material properties, consistent thickness and be physiological in behaviour.

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Prevention of CaCl2-induced aortic inflammation and subsequent aneurysm formation by the CCL3–CCR5 axis

Nature Communications ◽

10.1038/s41467-020-19763-0 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Yuko Ishida ◽

Yumi Kuninaka ◽

Mizuho Nosaka ◽

Akihiko Kimura ◽

Akira Taruya ◽

...

Keyword(s):

Abdominal Aortic Aneurysm ◽

Angiotensin Ii ◽

Aortic Aneurysm ◽

Abdominal Aorta ◽

Chemokine Receptor ◽

Wild Type ◽

Specific Receptor ◽

Cytokines And Chemokines ◽

Abdominal Aortic ◽

Enhanced Expression

AbstractInflammatory mediators such as cytokines and chemokines are crucially involved in the development of abdominal aortic aneurysm (AAA). Here we report that CaCl2 application into abdominal aorta induces AAA with intra-aortic infiltration of macrophages as well as enhanced expression of chemokine (C-C motif) ligand 3 (CCL3) and MMP-9. Moreover, infiltrating macrophages express C-C chemokine receptor 5 (CCR5, a specific receptor for CCL3) and MMP-9. Both Ccl3−/− mice and Ccr5−/− but not Ccr1−/− mice exhibit exaggerated CaCl2-inducced AAA with augmented macrophage infiltration and MMP-9 expression. Similar observations are also obtained on an angiotensin II-induced AAA model. Immunoneutralization of CCL3 mimics the phenotypes observed in CaCl2-treated Ccl3−/− mice. On the contrary, CCL3 treatment attenuates CaCl2-induced AAA in both wild-type and Ccl3−/− mice. Consistently, we find that the CCL3–CCR5 axis suppresses PMA-induced enhancement of MMP-9 expression in macrophages. Thus, CCL3 can be effective to prevent the development of CaCl2-induced AAA by suppressing MMP-9 expression.

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