Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Aug 8:5:296.
doi: 10.3389/fphys.2014.00296. eCollection 2014.

Adventitial inflammation and its interaction with intimal atherosclerotic lesions

Mohammadreza Akhavanpoor  1 , Susanne Wangler  1 , Christian A Gleissner  1 , Grigorios Korosoglou  1 , Hugo A Katus  1 , Christian Erbel  1
Affiliations
Review

Adventitial inflammation and its interaction with intimal atherosclerotic lesions

Mohammadreza Akhavanpoor et al. Front Physiol. .

Abstract

The presence of adventitial inflammation in correlation with atherosclerotic lesions has been recognized for decades. In the last years, several studies have investigated the relevance and impact of adventitial inflammation on atherogenesis. In the abdominal aorta of elderly Apoe(-/-) mice, adventitial inflammatory structures were characterized as organized ectopic lymphoid tissue, and therefore termed adventitial tertiary lymphoid organs (ATLOs). These ATLOs possess similarities in development, structure and function to secondary lymphoid organs. A crosstalk between intimal atherosclerotic lesions and ATLOs has been suggested, and several studies could demonstrate a potential role for medial vascular smooth muscle cells in this process. We here review the development, phenotypic characteristics, and function of ATLOs in atherosclerosis. Furthermore, we discuss the possible role of medial vascular smooth muscle cells and their interaction between plaque and ATLOs.

Keywords: adventitial inflammation; adventitial tertiary lymphoid organs; atherosclerosis; autoimmunity; macrophages; vascular smooth muscle cells.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Adventitial tertiary lymphoid organs (ATLOs) in atherosclerosis. The cellularity and structure of ATLOs in the diseased vessel wall is presented. ATLOs represent organized accumulation of different lymphoid cells, developed in response to the chronic inflammatory process of atherosclerosis. Stage III ATLOs show T and B cell areas. Germinal centers with follicular dendritic cells surrounded by centrocytes and B cells are present. Lymph vessels and high endothelial venules (HEV) facilitate the recruitment of lymphocytes from the blood into ATLOs. Similar to lymph nodes, ATLOs contain a mesenchymal network of conduits, connecting the lamina media with HEVs in T cell areas. Small molecular weight molecules (such as chemokines and cytokines) can be transported by these conduits. A cross-talk between the plaque and the ATLO via the medial VSMCs is postulated.
Figure 2
Figure 2
Adventitial inflammation in atherosclerosis. Intimal atherosclerotic lesions are frequently accompanied by an inflammatory process in the adjacent adventitia. This inflammatory process is characterized by infiltration of T cells, B cells and dendritic cells in the adventitia. In some cases T and B cell aggregations can be seen. There is a correlation between the size of the intimal lesion and the adventitial structures and a crosstalk between both compartments is suggested.
Figure 3
Figure 3
The possible role of VSMCs in the formation of Adventitial tertiary lymphoid organs (ATLOs). Pro-inflammatory cytokines (such as TNF and LTα1β2) activate VSMCs by TNFR-1 or LTßR signaling thereby inducing an LTo phenotype in VSMCs. Activated VSMCs express lymphorganogenic chemokines such as CCL19, CCL21, CXCL13, and CXCL16, thereby orchestrating ATLO neogenesis and developement. I, Intima; M, Media; A, Adventitia.
See this image and copyright information in PMC

References

    1. Aloisi F., Pujol-Borrell R. (2006). Lymphoid neogenesis in chronic inflammatory diseases. Nat. Rev. Immunol. 6, 205–217 10.1038/nri1786 - DOI - PubMed
    1. Armengol M. P., Juan M., Lucas-Martin A., Fernandez-Figueras M. T., Jaraquemada D., Gallart T., et al. (2001). Thyroid autoimmune disease: demonstration of thyroid antigen-specific B cells and recombination-activating gene expression in chemokine-containing active intrathyroidal germinal centers. Am. J. Pathol. 159, 861–873 10.1016/S0002-9440(10)61762-2 - DOI - PMC - PubMed
    1. Carragher D. M., Rangel-Moreno J., Randall T. D. (2008). Ectopic lymphoid tissues and local immunity. Semin. Immunol. 20, 26–42 10.1016/j.smim.2007.12.004 - DOI - PMC - PubMed
    1. Charo I. F., Ransohoff R. M. (2006). The many roles of chemokines and chemokine receptors in inflammation. N. Engl. J. Med. 354, 610–621 10.1056/NEJMra052723 - DOI - PubMed
    1. Chen S. C., Vassileva G., Kinsley D., Holzmann S., Manfra D., Wiekowski M. T., et al. (2002). Ectopic expression of the murine chemokines CCL21a and CCL21b induces the formation of lymph node-like structures in pancreas, but not skin, of transgenic mice. J. Immunol. 168, 1001–1008 10.4049/jimmunol.168.3.1001 - DOI - PubMed

LinkOut - more resources