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Myeloid Thrombomodulin Regulates Vascular Inflammation in Abdominal Aortic Aneurysm
Author(s) -
Wu HuaLin,
Wang KuanChieh,
Shi GueyYueh
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.888.7
Subject(s) - thrombomodulin , proinflammatory cytokine , inflammation , abdominal aortic aneurysm , medicine , angiotensin ii , macrophage , aortic aneurysm , endothelium , chemokine , immunology , aneurysm , pathology , chemistry , thrombin , in vitro , platelet , receptor , biochemistry , surgery
Thrombomodulin (TM) is originally described as a marker of endothelium and functions as an anti‐coagulant. Apart from its anticoagulant properties, we have recently reported that monocytic TM participated in pathogen‐induced inflammatory responses in experimental sepsis models. However, the contribution of TM to vascular inflammation in the development of cardiovascular diseases, such as abdominal aortic aneurysm (AAA), is still poorly understood. CaCl 2 ‐induced and angiotensin II‐infused experimental models of AAA were used to investigate the role of TM. Myeloid TM‐deficient mice (LysMcre/TM flox/flox ), not vascular smooth muscle cell TM‐deficient mice (SM22‐cre tg /TM flox/flox mice) exhibited significantly reduced levels of aneurysmal expansion, infiltrating macrophages, proinflammatory cytokines and matrix metalloproteinase‐9. Similar results were observed in the ApoE knock‐out TM‐deficient mice (ApoE ‐/‐ /LysMcre/TM flox/flox mice) with infusion of angiotensin II. Moreover, thioglycollate‐induced TM‐deficient macrophages displayed reduced proinflammatory cytokine profiles, oxidative stress, and adhesion to endothelial cells compared with wild‐type mice. Consistent with our observation in the CaCl 2 ‐treated murine aortas, we also demonstrated that TM was predominantly located in infiltrating macrophages in human AAA samples. Macrophage infiltration plays an important role in aortic aneurysm, whereas TM expression is involved in the inflammatory responses in macrophages. Decrease of TM expression in macrophages may suppress inflammatory response in vitro as well as aortic aneurysm. These results suggest that targeting to TM‐mediated inflammatory responses in monocytes/macrophages could be a new therapeutic target for AAA.