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. Author manuscript; available in PMC: 2014 Jun 5.
Published in final edited form as: Nature. 2012 May 16;485(7399):512–516. doi: 10.1038/nature11087

Figure 4. ApoE isoform-specific regulation of CypA-NF-kB-MMP-9 pathway in pericytes.

Figure 4

(a) CypA mRNA quantification in Apoe−/− pericytes after treatment with astrocyte-secreted apoE3, apoE4, siRNA silencing of LDL/apoE receptors and adenoviral-mediated re-expression of LRP1 minigene (Ad.m LRP1). Mean±s.e.m., n=3 independent cultures. (b) Proximity ligation imaging of apoE3 and apoE4 interaction with LRP1. (c–d) LRP1, CypA and MMP-9 immunodetection (c) and neuronal uptake (NeuN, green) of cadaverine-Alexa-Fluor-555 (red; yellow, merged) (d) in the hippocampus of 6-month-old GFAP-APOE3 mice after siLRP1 or control siRNA infusion. Blue, lectin-positive capillaries. (e) A schematic showing that astrocyte-secreted apoE3 and murine apoE, but not apoE4, signal to pericytes via LRP1 suppressing the CypA-NF-kB-MMP-9 pathway that causes BBB breakdown. b and c–d, representative results from 6 experiments.