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Anti-JNK2 peptide-siRNA nanostructures improve plaque endothelium and reduce thrombotic risk in atherosclerotic mice.


ABSTRACT:

Background

A direct and independent role of inflammation in atherothrombosis was recently highlighted by the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) trial, showing the benefit of inhibiting signaling molecules, eg, interleukins. Accordingly, we sought to devise a flexible platform for preventing the inflammatory drivers at their source to preserve plaque endothelium and mitigate procoagulant risk.

Methods

p5RHH-siRNA nanoparticles were formulated through self-assembly processes. The therapeutic efficacy of p5RHH-JNK2 siRNA nanoparticles was evaluated both in vitro and in vivo.

Results

Because JNK2 is critical to macrophage uptake of oxidized lipids through scavenger receptors that engender expression of myriad inflammatory molecules, we designed

SUBMITTER: Pan H 

PROVIDER: S-EPMC6135209 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature