Research ArticleAtherosclerosis

siRNA nanoparticles targeting CaMKIIγ in lesional macrophages improve atherosclerotic plaque stability in mice

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Science Translational Medicine  22 Jul 2020:
Vol. 12, Issue 553, eaay1063
DOI: 10.1126/scitranslmed.aay1063

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Perturbing plaque macrophages

Macrophages in atherosclerotic lesions promote inflammation and plaque progression and are an attractive therapeutic target. Here, Tao et al. used nanoparticles to inhibit pro-atherogenic macrophages by siRNA targeting Ca2+/calmodulin-dependent protein kinase γ. Nanoparticle treatment induced phagocytosis of apoptotic cells in plaques and promoted plaque stability, reducing necrotic area and increasing fibrous cap thickness in a mouse model of atherosclerosis. This study establishes proof of concept for siRNA nanoparticles targeting lesional macrophages as a treatment for atherosclerosis.

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