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Targeted nanoparticles containing the proresolving peptide Ac2-26 protect against advanced atherosclerosis in hypercholesterolemic mice.
- Source :
-
Science translational medicine [Sci Transl Med] 2015 Feb 18; Vol. 7 (275), pp. 275ra20. - Publication Year :
- 2015
-
Abstract
- Chronic, nonresolving inflammation is a critical factor in the clinical progression of advanced atherosclerotic lesions. In the normal inflammatory response, resolution is mediated by several agonists, among which is the glucocorticoid-regulated protein called annexin A1. The proresolving actions of annexin A1, which are mediated through its receptor N-formyl peptide receptor 2 (FPR2/ALX), can be mimicked by an amino-terminal peptide encompassing amino acids 2-26 (Ac2-26). Collagen IV (Col IV)-targeted nanoparticles (NPs) containing Ac2-26 were evaluated for their therapeutic effect on chronic, advanced atherosclerosis in fat-fed Ldlr(-/-) mice. When administered to mice with preexisting lesions, Col IV-Ac2-26 NPs were targeted to lesions and led to a marked improvement in key advanced plaque properties, including an increase in the protective collagen layer overlying lesions (which was associated with a decrease in lesional collagenase activity), suppression of oxidative stress, and a decrease in plaque necrosis. In mice lacking FPR2/ALX in myeloid cells, these improvements were not seen. Thus, administration of a resolution-mediating peptide in a targeted NP activates its receptor on myeloid cells to stabilize advanced atherosclerotic lesions. These findings support the concept that defective inflammation resolution plays a role in advanced atherosclerosis, and suggest a new form of therapy.<br /> (Copyright © 2015, American Association for the Advancement of Science.)
- Subjects :
- Animals
Atherosclerosis complications
Atherosclerosis metabolism
Collagen Type IV metabolism
Hypercholesterolemia metabolism
Mice
Mice, Knockout
Oxidative Stress
Receptors, LDL genetics
Receptors, LDL physiology
Annexin A1 pharmacology
Atherosclerosis prevention & control
Hypercholesterolemia complications
Nanoparticles
Peptides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1946-6242
- Volume :
- 7
- Issue :
- 275
- Database :
- MEDLINE
- Journal :
- Science translational medicine
- Publication Type :
- Academic Journal
- Accession number :
- 25695999
- Full Text :
- https://doi.org/10.1126/scitranslmed.aaa1065