RNAi targeting multiple cell adhesion molecules reduces immune cell recruitment and vascular inflammation after myocardial infarction
Name
Anderson_RNAi targeting.pdf
Size
3.03 MB
Format
Adobe PDF
Checksum (MD5)
08449f39e5af5edabc582f039e85174d
Author(s)
Sager, H. B.
Dutta, P.
Hulsmans, M.
Courties, G.
Sun, Y.
Heidt, T.
Vinegoni, C.
Borodovsky, A.
Fitzgerald, K.
Wojtkiewicz, G. R.
Date Issued
June 2016
Journal
Science Translational Medicine
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Sager, H. B. et al. “RNAi Targeting Multiple Cell Adhesion Molecules Reduces Immune Cell Recruitment and Vascular Inflammation after Myocardial Infarction.” Science Translational Medicine 8.342 (2016): 342ra80-342ra80.
Version
Author's final manuscript
Abstract
Myocardial infarction (MI) leads to a systemic surge of vascular inflammation in mice and humans, resulting in secondary ischemic complications and high mortality. We show that, in ApoE−/− mice with coronary ligation, increased sympathetic tone up-regulates not only hematopoietic leukocyte production but also plaque endothelial expression of adhesion molecules. To counteract the resulting arterial leukocyte recruitment, we developed nanoparticle-based RNA interference (RNAi) that effectively silences five key adhesion molecules. Simultaneously encapsulating small interfering RNA (siRNA)–targeting intercellular cell adhesion molecules 1 and 2 (Icam1 and Icam2), vascular cell adhesion molecule 1 (Vcam1), and E- and P-selectins (Sele and Selp) into polymeric endothelial-avid nanoparticles reduced post-MI neutrophil and monocyte recruitment into atherosclerotic lesions and decreased matrix-degrading plaque protease activity. Five-gene combination RNAi also curtailed leukocyte recruitment to ischemic myocardium. Therefore, targeted multigene silencing may prevent complications after acute MI.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1126/scitranslmed.aaf1435
