Research ArticleCardiovascular Disease

Targeted nanoparticles containing the proresolving peptide Ac2-26 protect against advanced atherosclerosis in hypercholesterolemic mice

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Science Translational Medicine  18 Feb 2015:
Vol. 7, Issue 275, pp. 275ra20
DOI: 10.1126/scitranslmed.aaa1065

Inflammation resolution: A solution for advanced atherosclerosis

In atherosclerosis, fatty plaques build up in the arteries. It is therefore common that people with cardiovascular disease at risk for atherosclerosis will take statins, or lipid-lowering drugs. However, a complementary approach may be to resolve the ongoing, chronic inflammation in atherosclerosis. Such a proresolving tactic was adopted by Fredman et al. The authors encapsulated 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. Once in place, the particles slowly released Ac2-26, which bound to immune cells, reducing oxidative stress, promoting collagen buildup, and increasing the anti-inflammatory cytokine interleukin-10—in sum, working to resolve inflammation and stabilize the plaque. This new proresolving nanomedicine approach will need to be tested in larger vessels and in animal models more similar to human atherosclerosis. But this targeted therapy is a first of its kind, paving the way for a new type of therapy to prevent heart disease.