Nanoparticle-Mediated Delivery of Pitavastatin Inhibits Atherosclerotic Plaque Destabilization/Rupture in Mice by Regulating the Recruitment of Inflammatory Monocytes
Abstract
Background—: Preventing atherosclerotic plaque destabilization and rupture is the most reasonable therapeutic strategy for acute myocardial infarction. Therefore, we tested the hypotheses that (1) inflammatory monocytes play a causative role in plaque destabilization and rupture and (2) the nanoparticle-mediated delivery of pitavastatin into circulating inflammatory monocytes inhibits plaque destabilization and rupture. Methods and Results—: We used a model of plaque destabilization and rupture in the brachiocephalic arteries of apolipoprotein E–deficient (ApoE −/− ) mice fed a high-fat diet and infused with angiotensin II. The adoptive transfer of CCR2 +/+ Ly-6C high inflammatory macrophages, but not CCR2 −/− leukocytes, accelerated plaque destabilization associated with increased serum monocyte chemoattractant protein-1 (MCP-1), monocyte-colony stimulating factor, and matrix metalloproteinase-9. We prepared poly(lactic-co-glycolic) acid nanoparticles that were incorporated by Ly-6G − CD11b + monocytes and delivered into atherosclerotic plaques after intravenous administration. Intravenous treatment with pitavastatin-incorporated nanoparticles, but not with control nanoparticles or pitavastatin alone, inhibited plaque destabilization and rupture associated with decreased monocyte infiltration and gelatinase activity in the plaque. Pitavastatin-incorporated nanoparticles inhibited MCP-1–induced monocyte chemotaxis and the secretion of MCP-1 and matrix metalloproteinase-9 from cultured macrophages. Furthermore, the nanoparticle-mediated anti–MCP-1 gene therapy reduced the incidence of plaque destabilization and rupture. Conclusions—: The recruitment of inflammatory monocytes is critical in the pathogenesis of plaque destabilization and rupture, and nanoparticle-mediated pitavastatin delivery is a promising therapeutic strategy to inhibit plaque destabilization and rupture by regulating MCP-1/CCR2–dependent monocyte recruitment in this model.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
FTIC-loaded PLGA nanoparticles could be delivered to atherosclerotic sites via enhanced permeability and phagocytosis by monocytes and macrophages.
“Such imaging-based diagnosis could be achieved by FTIC-loaded PLGA nanoparticles, which could be delivered to atherosclerotic sites, most likely via enhanced permeability in the atherosclerotic lesions and mechanistically through phagocytosis by monocytes and macrophages.157”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [157]
Pitavastatin embedded in PLGA-NPs reduced plaque destabilization/rupture by reducing Ly6Chigh monocytes and macrophage infiltration via MCP-1/CCR2 signaling.
“Furthermore, pitavastatin (HMG-CoA reductase inhibitor) embedded in PLGA-NPs reduced plaque destabilization/rupture by reducing the circulation of Ly6Chigh monocytes and the infiltration of macrophages into atherosclerotic lesions by interfering with MCP-1/CCR2 signaling-mediated monocyte recruitment.157”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [157]
The citation lists haven’t been fetched yet
References 51 · Cited by 179
- Authors
- Katsuki, S., Matoba, T., Nakashiro, S., Sato, K., Koga, J.-I., Nakano, K., Nakano, Y., Egusa, S., Sunagawa, K., & Egashira, K.
- Affiliations
- Kyushu University (JP)
- Venue
- Circulation
- Published
- 2014-02-25
- Volume
- 129
- Issue
- 8
- Pages
- 896-906
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2063704757
- Cited by
- 179
- References
- 51
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 15 · 2023: 8 · 2022: 20 · 2021: 18 · 2020: 15 · 2019: 21 · 2018: 13 · 2017: 15 · 2016: 18 · 2015: 9 · 2014: 5
- FWCI
- 5.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Kyushu University Institutional Repository (QIR) (Kyushu University) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- pitavastatin, nanoparticle drug delivery, atherosclerotic plaque destabilization, plaque rupture, inflammatory monocytes, CCR2, MCP-1, MMP-9, PLGA nanoparticles, acute myocardial infarction, ApoE-deficient mice, high-fat diet, angiotensin II, monocyte recruitment
- MeSH terms
- Animals, Apolipoproteins E, Cell Movement, Disease Models, Animal, Male, Mice, Inbred C57BL, Monocytes, Quinolines, Genetic Therapy, Brachiocephalic Trunk, Drug Delivery Systems, Mice, Knockout, Chemokine CCL2, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Adoptive Transfer, Mice, Nanoparticles, Receptors, CCR2, Mice, 129 Strain, Plaque, Atherosclerotic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
