| Title |
RNAi targeting multiple cell adhesion molecules reduces immune cell recruitment and vascular inflammation after myocardial infarction
|
|---|---|
| Published in |
Science Translational Medicine, June 2016
|
| DOI | 10.1126/scitranslmed.aaf1435 |
| Pubmed ID | |
| Authors |
Hendrik B Sager, Partha Dutta, James E Dahlman, Maarten Hulsmans, Gabriel Courties, Yuan Sun, Timo Heidt, Claudio Vinegoni, Anna Borodovsky, Kevin Fitzgerald, Gregory R Wojtkiewicz, Yoshiko Iwamoto, Benoit Tricot, Omar F Khan, Kevin J Kauffman, Yiping Xing, Taylor E Shaw, Peter Libby, Robert Langer, Ralph Weissleder, Filip K Swirski, Daniel G Anderson, Matthias Nahrendorf |
| 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. |
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X Demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
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| India | 2 | 4% |
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| Korea, Republic of | 1 | 2% |
| Indonesia | 1 | 2% |
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| Other | 2 | 4% |
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Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 38 | 67% |
| Scientists | 10 | 18% |
| Science communicators (journalists, bloggers, editors) | 5 | 9% |
| Practitioners (doctors, other healthcare professionals) | 4 | 7% |
Mendeley demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 1% |
| Sweden | 1 | <1% |
| Germany | 1 | <1% |
| Brazil | 1 | <1% |
| Unknown | 181 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 38 | 20% |
| Researcher | 34 | 18% |
| Student > Bachelor | 16 | 9% |
| Student > Doctoral Student | 15 | 8% |
| Student > Master | 15 | 8% |
| Other | 17 | 9% |
| Unknown | 51 | 27% |
| Readers by discipline | Count | As % |
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| Agricultural and Biological Sciences | 24 | 13% |
| Engineering | 11 | 6% |
| Immunology and Microbiology | 8 | 4% |
| Other | 25 | 13% |
| Unknown | 59 | 32% |