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IL-7R blockade reduces post-myocardial infarction-induced atherosclerotic plaque inflammation in ApoE-/- mice.


ABSTRACT: Modulating inflammation by targeting IL-1? reduces recurrent athero-thrombotic cardiovascular events without lipid lowering. This presents an opportunity to explore other pathways associated with the IL-1? signaling cascade to modulate the inflammatory response post-myocardial infarction (MI). IL-7 is a mediator of the inflammatory pathway involved in monocyte trafficking into atherosclerotic plaques and levels of IL-7 have been shown to be elevated in patients with acute MI. Recurrent athero-thrombotic events are believed to be mediated in part by index MI-induced exacerbation of inflammation in atherosclerotic plaques. The objective of the study was to assess the feasibility of IL-7R blockade to modulate atherosclerotic plaque inflammation following acute MI in ApoE-/- mice. Mice were fed Western diet for 12 weeks and then subjected to coronary occlusion to induce an acute MI. IL-7 expression was determined using qRT-PCR and immuno-staining, and IL-7R was assessed using flow cytometry. Plaque inflammation was evaluated using immunohistochemistry. IL-7R blockade was accomplished with monoclonal antibody to IL-7R. IL-7 mRNA expression was significantly increased in the cardiac tissue of mice subjected to MI but not in controls. IL-7 staining was observed in the coronary artery. Plaque macrophage and lipid content were significantly increased after MI. IL-7R antibody treatment but not control IgG significantly reduced macrophage and lipid content in atherosclerotic plaques. The results show that IL-7R antibody treatment reduces monocyte/macrophage and lipid content in the atherosclerotic plaque following MI suggesting a potential new target to mitigate increased plaque inflammation post-MI.

SUBMITTER: Mihailovic PM 

PROVIDER: S-EPMC6517313 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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IL-7R blockade reduces post-myocardial infarction-induced atherosclerotic plaque inflammation in ApoE<sup>-/-</sup> mice.

Mihailovic Peter M PM   Lio Wai Man WM   Yano Juliana J   Zhou Jianchang J   Zhao Xiaoning X   Chyu Kuang-Yuh KY   Shah Prediman K PK   Cercek Bojan B   Dimayuga Paul C PC  

Biochemistry and biophysics reports 20190513


Modulating inflammation by targeting IL-1β reduces recurrent athero-thrombotic cardiovascular events without lipid lowering. This presents an opportunity to explore other pathways associated with the IL-1β signaling cascade to modulate the inflammatory response post-myocardial infarction (MI). IL-7 is a mediator of the inflammatory pathway involved in monocyte trafficking into atherosclerotic plaques and levels of IL-7 have been shown to be elevated in patients with acute MI. Recurrent athero-th  ...[more]

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