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Adventitial inflammation and its interaction with intimal atherosclerotic lesions.

Akhavanpoor M, Wangler S, Gleissner CA, Korosoglou G, Katus HA, Erbel C - Front Physiol (2014)

Bottom Line: 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.Furthermore, we discuss the possible role of medial vascular smooth muscle cells and their interaction between plaque and ATLOs.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, University of Heidelberg Heidelberg, Germany ; DZHK (German Centre for Cardiovascular Research) Partner Site Heidelberg/Mannheim, Germany.

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.

No MeSH data available.


Related in: MedlinePlus

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.
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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.

Mentions: Based on the above mentioned data, there seems to be a communication between the atherosclerotic lesion in the intima and TLOs in the adventitia. Since both compartments of the arterial wall are separated by vascular smooth muscle cells (VSCMs) in the lamina media, it is likely that these VSMCs coordinate the communication between both compartments. The direct traffic of inflammatory cells through the smooth muscle layer of the lamina media is limited (Dal Canto et al., 2001). As (Gräbner et al., 2009) demonstrated, medial VSMCs surrounded by intimal plaque and ATLOs were able to express the chemokines CXCL13 and CCL21 through the LTßR-dependent signaling pathway (Gräbner et al., 2009). CXCL13 and CCL21 are both lymphorganogenic chemokines that are involved in the formation of secondary and tertiary lymphoid organs (Luster, 1998; Luther et al., 2000; Chen et al., 2002; Cupedo and Mebius, 2005; Charo and Ransohoff, 2006). Gräbner et al. suggested that activated VSCMs underlying atherosclerotic lesion develop properties of LTo cells and thereby induce ATLO neogenesis (Gräbner et al., 2009). LTos are described as mesenchymal cells that control embryonic lymph node development (Luther et al., 2002; Mebius, 2003; Carragher et al., 2008). In 2010, Lotzer et al. supported the hypothesis that VSMCs may differentiate into LTo cells (Lotzer et al., 2010). Simultaneous stimulation of mouse aortic smooth muscle cells by TNF-α and LTßR signaling induced expression of several homeostatic and lymphorganogenic chemokines, which are thought to promote the recruitment of leukocytes to the adventitia and thereby enable the formation of ATLOs (Lotzer et al., 2010). Furthermore, Gräbner et al. could recognize lymph node like conduits connecting medial VSMCs to ATLOs (Gräbner et al., 2009); low molecular weight molecules can be transported into ATLOs via these conduits (Gräbner et al., 2009). In lymph nodes, similar conduits connect afferent lymph vessels and high endothelial venules, coordinating the transport of antigens into lymph nodes (Itano and Jenkins, 2003; Sixt et al., 2005). During the development of secondary lymphoid organs, LTo cells are activated by lymphoid tissue inducer cells (Mebius, 2003). In 2014, Guedj et al. demonstrated the capability of M1 macrophages to act as LTi cells triggering the differentiation of VSMCs into LTo cells (Guedj et al., 2014). They suggest that the interaction between M1 macrophages and VSMCs may induce ATLO formation (Guedj et al., 2014). Taken together, all data published up to date suggest that VSMCs may be involved in ATLO development and interaction of atherosclerotic lesions with ATLOs. Figure 3 demonstrates the possible role of VSMCs in the lamina media between ATLOs and atherosclerotic lesions in the development of ATLOs.


Adventitial inflammation and its interaction with intimal atherosclerotic lesions.

Akhavanpoor M, Wangler S, Gleissner CA, Korosoglou G, Katus HA, Erbel C - Front Physiol (2014)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126462&req=5

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.
Mentions: Based on the above mentioned data, there seems to be a communication between the atherosclerotic lesion in the intima and TLOs in the adventitia. Since both compartments of the arterial wall are separated by vascular smooth muscle cells (VSCMs) in the lamina media, it is likely that these VSMCs coordinate the communication between both compartments. The direct traffic of inflammatory cells through the smooth muscle layer of the lamina media is limited (Dal Canto et al., 2001). As (Gräbner et al., 2009) demonstrated, medial VSMCs surrounded by intimal plaque and ATLOs were able to express the chemokines CXCL13 and CCL21 through the LTßR-dependent signaling pathway (Gräbner et al., 2009). CXCL13 and CCL21 are both lymphorganogenic chemokines that are involved in the formation of secondary and tertiary lymphoid organs (Luster, 1998; Luther et al., 2000; Chen et al., 2002; Cupedo and Mebius, 2005; Charo and Ransohoff, 2006). Gräbner et al. suggested that activated VSCMs underlying atherosclerotic lesion develop properties of LTo cells and thereby induce ATLO neogenesis (Gräbner et al., 2009). LTos are described as mesenchymal cells that control embryonic lymph node development (Luther et al., 2002; Mebius, 2003; Carragher et al., 2008). In 2010, Lotzer et al. supported the hypothesis that VSMCs may differentiate into LTo cells (Lotzer et al., 2010). Simultaneous stimulation of mouse aortic smooth muscle cells by TNF-α and LTßR signaling induced expression of several homeostatic and lymphorganogenic chemokines, which are thought to promote the recruitment of leukocytes to the adventitia and thereby enable the formation of ATLOs (Lotzer et al., 2010). Furthermore, Gräbner et al. could recognize lymph node like conduits connecting medial VSMCs to ATLOs (Gräbner et al., 2009); low molecular weight molecules can be transported into ATLOs via these conduits (Gräbner et al., 2009). In lymph nodes, similar conduits connect afferent lymph vessels and high endothelial venules, coordinating the transport of antigens into lymph nodes (Itano and Jenkins, 2003; Sixt et al., 2005). During the development of secondary lymphoid organs, LTo cells are activated by lymphoid tissue inducer cells (Mebius, 2003). In 2014, Guedj et al. demonstrated the capability of M1 macrophages to act as LTi cells triggering the differentiation of VSMCs into LTo cells (Guedj et al., 2014). They suggest that the interaction between M1 macrophages and VSMCs may induce ATLO formation (Guedj et al., 2014). Taken together, all data published up to date suggest that VSMCs may be involved in ATLO development and interaction of atherosclerotic lesions with ATLOs. Figure 3 demonstrates the possible role of VSMCs in the lamina media between ATLOs and atherosclerotic lesions in the development of ATLOs.

Bottom Line: 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.Furthermore, we discuss the possible role of medial vascular smooth muscle cells and their interaction between plaque and ATLOs.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, University of Heidelberg Heidelberg, Germany ; DZHK (German Centre for Cardiovascular Research) Partner Site Heidelberg/Mannheim, Germany.

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.

No MeSH data available.


Related in: MedlinePlus