TITLE

CD137-CD137L Interaction Regulates Atherosclerosis via Cyclophilin A in Apolipoprotein E-Deficient Mice

AUTHOR(S)
Li, Yuefeng; Yan, Jinchuan; Wu, Chao; Wang, Zhongqun; Yuan, Wei; Wang, Dongqing
PUB. DATE
February 2014
SOURCE
PLoS ONE;Feb2014, Vol. 9 Issue 2, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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.
ACCESSION #
94730272

 

Related Articles

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics