The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Monocyte-Directed RNAi Targeting CCR2 Improves Infarct Healing in Atherosclerosis-Prone Mice
Open accessAbstract
Background—: Exaggerated and prolonged inflammation after myocardial infarction (MI) accelerates left ventricular remodeling. Inflammatory pathways may present a therapeutic target to prevent post-MI heart failure. However, the appropriate magnitude and timing of interventions are largely unknown, in part because noninvasive monitoring tools are lacking. Here, we used nanoparticle-facilitated silencing of CCR2, the chemokine receptor that governs inflammatory Ly-6C high monocyte subset traffic, to reduce infarct inflammation in apolipoprotein E–deficient (apoE −/− ) mice after MI. We used dual-target positron emission tomography/magnetic resonance imaging of transglutaminase factor XIII (FXIII) and myeloperoxidase (MPO) activity to monitor how monocyte subset–targeted RNAi altered infarct inflammation and healing. Methods and Results—: Flow cytometry, gene expression analysis, and histology revealed reduced monocyte numbers and enhanced resolution of inflammation in infarcted hearts of apoE −/− mice that were treated with nanoparticle-encapsulated siRNA. To follow extracellular matrix cross-linking noninvasively, we developed a fluorine-18–labeled positron emission tomography agent ( 18 F-FXIII). Recruitment of MPO-rich inflammatory leukocytes was imaged with a molecular magnetic resonance imaging sensor of MPO activity (MPO-Gd). Positron emission tomography/magnetic resonance imaging detected anti-inflammatory effects of intravenous nanoparticle-facilitated siRNA therapy (75% decrease of MPO-Gd signal; P <0.05), whereas 18 F-FXIII positron emission tomography reflected unimpeded matrix cross-linking in the infarct. Silencing of CCR2 during the first week after MI improved ejection fraction on day 21 after MI from 29% to 35% ( P <0.05). Conclusion—: CCR2-targeted RNAi reduced recruitment of Ly-6C high monocytes, attenuated infarct inflammation, and curbed post-MI left ventricular remodeling.
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Cites
Knocking down barriers: advances in siRNA delivery
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Self-citationThe inflammatory response in myocardial infarction
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Self-citationMyocardial infarction accelerates atherosclerosis
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Self-citationTherapeutic siRNA silencing in inflammatory monocytes in mice
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Self-citationMonocytes: Protagonists of Infarct Inflammation and Repair After Myocardial Infarction
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Self-citationImaging of atherosclerotic cardiovascular disease
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Targeting inflammation in atherosclerosis — from experimental insights to the clinic
Soehnlein, O., & Libby, P. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00198-1 · Cited by 1,019
Self-Renewing Resident Cardiac Macrophages Limit Adverse Remodeling Following Myocardial Infarction
Dick, S. A., Macklin, J. A., Nejat, S., Momen, A., Clemente-Casares, X., Althagafi, M. G., Chen, J., Kantores, C., Hosseinzadeh, S., Aronoff, L., et al. (2019) · Nature Immunology · doi:10.1038/s41590-018-0272-2 · Cited by 883
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Heidt, T., Courties, G., Dutta, P., Sager, H. B., Sebas, M., Iwamoto, Y., Sun, Y., Da Silva, N., Panizzi, P., van der Laan, A. M., et al. (2014) · Circulation Research · doi:10.1161/circresaha.115.303567 · Cited by 607
Self-citationCardiac monocytes and macrophages after myocardial infarction
Peet, C., Ivetic, A., Bromage, D. I., & Shah, A. M. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvz336 · Cited by 600
Metadata
- Authors
- Majmudar, M. D., Keliher, E. J., Heidt, T., Leuschner, F., Truelove, J., Sena, B. F., Gorbatov, R., Iwamoto, Y., Dutta, P., Wojtkiewicz, G., Courties, G., Sebas, M., Borodovsky, A., Fitzgerald, K., Nolte, M. W., Dickneite, G., Chen, J. W., Anderson, D. G., Swirski, F. K., Weissleder, R., & Nahrendorf, M.
- Venue
- Circulation
- Published
- 2013-05-21
- Volume
- 127
- Issue
- 20
- Pages
- 2038-2046
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W1576824462
- Cited by
- 292
- References
- 44
- FWCI
- 18.01
- Type
- journal article
- Language
- en
- Open access
- green
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- Majmudar, M. D., Keliher, E. J., Heidt, T., Leuschner, F., Truelove, J., Sena, B. F., Gorbatov, R., Iwamoto, Y., Dutta, P., Wojtkiewicz, G., Courties, G., Sebas, M., Borodovsky, A., Fitzgerald, K., Nolte, M. W., Dickneite, G., Chen, J. W., Anderson, D. G., Swirski, F. K., . . . Nahrendorf, M. (2013). Monocyte-Directed RNAi Targeting CCR2 Improves Infarct Healing in Atherosclerosis-Prone Mice. Circulation. https://doi.org/10.1161/circulationaha.112.000116
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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