Prostaglandin E2–EP2–NF-κB signaling in macrophages as a potential therapeutic target for intracranial aneurysms

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Sci. Signal.  07 Feb 2017:
Vol. 10, Issue 465, eaah6037
DOI: 10.1126/scisignal.aah6037

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A receptor target for intracranial aneurysms

The rupture of intracranial aneurysms is life-threatening. Unfortunately, surgery is currently the only therapeutic option. Inflammation mediated by macrophages that infiltrate the arterial wall both causes intracranial aneurysms and promotes their progression. Aoki et al. delineated a self-amplifying signaling pathway in macrophages that would be expected to aggravate the inflammation that underlies the formation and progression of intracranial aneurysms. They found that signaling through the prostaglandin E receptor subtype 2 (EP2) activated the transcription factor NF-κB to induce the expression of the genes encoding COX-2, the enzyme that synthesizes the ligand for EP2, and MCP-1, an attractant for macrophages. Administering an EP2 antagonist to rats prevented the formation and progression of intracranial aneurysms, suggesting that targeting the EP2 receptor could be a pharmacological alternative to treat developing intracranial aneurysms.