Editors' ChoicePharmacology

Inflammation resolution: A solution for advanced atherosclerosis

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Science Signaling  24 Feb 2015:
Vol. 8, Issue 365, pp. ec43
DOI: 10.1126/scisignal.aaa9573

In atherosclerosis, fatty plaques build up in the arteries, thus a common therapeutic strategy is lipid-lowering drugs. However, an alternative approach may be to resolve the ongoing, chronic inflammation in atherosclerosis. Fredman et al. encapsulated amino acids 2–26 (Ac2-26)—a small fragment of annexin A1, a protein that promotes the resolution of inflammation—in a polymeric nanoparticle and decorated the nanoparticle with a collagen IV–binding peptide, to target the therapeutic package to advanced atherosclerotic plaques. The Ac2-26 nanoparticles accumulated at vessel lesions in a mouse model of advanced atherosclerosis. The particles slowly released Ac2-26, which bound to immune cells, reducing oxidative stress, promoting collagen accumulation, and increasing the abundance of the anti-inflammatory cytokine interleukin-10, all of which contribute to resolving inflammation and stabilizing the plaque. This approach paves the way for a new type of therapy to prevent diseases arising from atherosclerosis and the instability of these clots that can lead to vessel occlusion in the brain (stroke) and heart (myocardial infarction).

G. Fredman, N. Kamaly, S. Spolitu, J. Milton, D. Ghorpade, R. Chiasson, G. Kuriakose, M. Perretti, O. Farokzhad, I. Tabas, Targeted nanoparticles containing the proresolving peptide Ac2-26 protect against advanced atherosclerosis in hypercholesterolemic mice. Sci. Transl. Med. 7, 275ra20 (2015). [Abstract]