CD137-CD137L interaction regulates atherosclerosis via cyclophilin A in apolipoprotein E-deficient mice.
BACKGROUND: Our previous studies showed that increased levels of cyclophilin A (CyPA) may be a valuable marker for predicting the severity of acute coronary syndromes and that interruption of CD137-CD137L interactions diminished the formation and progression of atherosclerosis in apolipoprotein E-de...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3919780?pdf=render |
| _version_ | 1818153202692915200 |
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| author | Yuefeng Li Jinchuan Yan Chao Wu Zhongqun Wang Wei Yuan Dongqing Wang |
| author_facet | Yuefeng Li Jinchuan Yan Chao Wu Zhongqun Wang Wei Yuan Dongqing Wang |
| author_sort | Yuefeng Li |
| collection | DOAJ |
| description | BACKGROUND: Our previous studies showed that increased levels of cyclophilin A (CyPA) may be a valuable marker for predicting the severity of acute coronary syndromes and that interruption of CD137-CD137L interactions diminished the formation and progression of atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice. Here, we sought to determine whether the proinflammatory factor CyPA is involved in atherosclerosis regulated by CD137-CD137L interactions. METHODS AND RESULTS: A constrictive collar was placed around the right carotid arteries of ApoE-/- mice that were fed a high-fat diet to induce atherosclerotic plaque formation. After that, the mice were intraperitoneally injected with anti-CD137 or anti-CD137L in the presence or absence of the recombinant lentiviral vectors LVTHM-CyPA or pGC-FU-CyPA, respectively. Interestingly, activation of CD137-CD137L was negatively correlated with CyPA expression in vivo and in vitro. Stimulating CD137-CD137L interaction significantly increased CyPA, which was concurrent with the upregulation of proinflammatory cytokines, chemokines and matrix metalloproteinases and resulted in the promotion of atherosclerosis in ApoE-/- mice. Silencing CyPA could eliminate these effects, and restoration of CyPA effectively and consistently attenuated the atherosclerotic suppression phenotypes elicited by the blockade of CD137-CD137L. CONCLUSION: These observations suggest that CD137-CD137L interactions mediated via regulation of CyPA contribute to the progression of atherosclerosis. |
| first_indexed | 2024-12-11T14:06:52Z |
| format | Article |
| id | doaj.art-d7e5c156b33742b4a380a81bb825b8d9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T14:06:52Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d7e5c156b33742b4a380a81bb825b8d92022-12-22T01:03:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e8856310.1371/journal.pone.0088563CD137-CD137L interaction regulates atherosclerosis via cyclophilin A in apolipoprotein E-deficient mice.Yuefeng LiJinchuan YanChao WuZhongqun WangWei YuanDongqing WangBACKGROUND: Our previous studies showed that increased levels of cyclophilin A (CyPA) may be a valuable marker for predicting the severity of acute coronary syndromes and that interruption of CD137-CD137L interactions diminished the formation and progression of atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice. Here, we sought to determine whether the proinflammatory factor CyPA is involved in atherosclerosis regulated by CD137-CD137L interactions. METHODS AND RESULTS: A constrictive collar was placed around the right carotid arteries of ApoE-/- mice that were fed a high-fat diet to induce atherosclerotic plaque formation. After that, the mice were intraperitoneally injected with anti-CD137 or anti-CD137L in the presence or absence of the recombinant lentiviral vectors LVTHM-CyPA or pGC-FU-CyPA, respectively. Interestingly, activation of CD137-CD137L was negatively correlated with CyPA expression in vivo and in vitro. Stimulating CD137-CD137L interaction significantly increased CyPA, which was concurrent with the upregulation of proinflammatory cytokines, chemokines and matrix metalloproteinases and resulted in the promotion of atherosclerosis in ApoE-/- mice. Silencing CyPA could eliminate these effects, and restoration of CyPA effectively and consistently attenuated the atherosclerotic suppression phenotypes elicited by the blockade of CD137-CD137L. CONCLUSION: These observations suggest that CD137-CD137L interactions mediated via regulation of CyPA contribute to the progression of atherosclerosis.http://europepmc.org/articles/PMC3919780?pdf=render |
| spellingShingle | Yuefeng Li Jinchuan Yan Chao Wu Zhongqun Wang Wei Yuan Dongqing Wang CD137-CD137L interaction regulates atherosclerosis via cyclophilin A in apolipoprotein E-deficient mice. PLoS ONE |
| title | CD137-CD137L interaction regulates atherosclerosis via cyclophilin A in apolipoprotein E-deficient mice. |
| title_full | CD137-CD137L interaction regulates atherosclerosis via cyclophilin A in apolipoprotein E-deficient mice. |
| title_fullStr | CD137-CD137L interaction regulates atherosclerosis via cyclophilin A in apolipoprotein E-deficient mice. |
| title_full_unstemmed | CD137-CD137L interaction regulates atherosclerosis via cyclophilin A in apolipoprotein E-deficient mice. |
| title_short | CD137-CD137L interaction regulates atherosclerosis via cyclophilin A in apolipoprotein E-deficient mice. |
| title_sort | cd137 cd137l interaction regulates atherosclerosis via cyclophilin a in apolipoprotein e deficient mice |
| url | http://europepmc.org/articles/PMC3919780?pdf=render |
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