CD137 Signaling Promotes Endothelial Apoptosis by Inhibiting Nrf2 Pathway, and Upregulating NF-κB Pathway

Figure 6

CD137 signaling accelerates endothelial cells apoptosis in vivo and in vitro, the Nrf2 and NF-κB pathway play protective role in this process. (a) ApoE^−/− mice were fed a high-fat diet and treated with agonist-CD137 recombinant protein or/and M5580, CAPE for 4 weeks. Immunofluorescence staining of CD31 (Alexa Fluor 594 stained (red)), TUNEL stain (green), and nucleus (DAPI stained (blue)) in aortas of ApoE^−/− mice. Scale bars represent 50 μm in ×400 magnifications. Boxed areas are shown at higher magnification in the panel aside them. Arrows indicate positivity for both CD31 and apoptotic cells. HFD indicates high-fat diet. (b) The expression of Bcl-2, Bax, and Cleaved Caspase-3 in aortas of ApoE^−/− mice were detected by Western blot analysis. (c) Apoptosis of HUVECs was detected by Annexin V/PI double-staining Flow cytometry. (d) Summarized data. (e) Western blot analysis determined expression of apoptosis-related proteins Bcl-2, Bax, and Cleaved Caspase-3 in HUVECs. Values are presented as the from three independent experiments. , , vs. control; ^#, ^##, ^### vs. agonist-CD137 group.

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