PMID- 24305567
OWN - NLM
STAT- MEDLINE
DCOM- 20140428
LR  - 20140225
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 129
IP  - 8
DP  - 2014 Feb 25
TI  - Nanoparticle-mediated delivery of pitavastatin inhibits atherosclerotic plaque 
      destabilization/rupture in mice by regulating the recruitment of inflammatory 
      monocytes.
PG  - 896-906
LID - 10.1161/CIRCULATIONAHA.113.002870 [doi]
AB  - 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.
FAU - Katsuki, Shunsuke
AU  - Katsuki S
AD  - Department of Cardiovascular Medicine (S.K., T.M., S.N., J.K., Y.N., S.E., K. 
      Sunagawa) and Department of Cardiovascular Research, Development, and 
      Translational Medicine (K. Sato, K.N., K.E.), Kyushu University Graduate School 
      of Medical Sciences, Fukuoka, Japan.
FAU - Matoba, Tetsuya
AU  - Matoba T
FAU - Nakashiro, Soichi
AU  - Nakashiro S
FAU - Sato, Kei
AU  - Sato K
FAU - Koga, Jun-ichiro
AU  - Koga J
FAU - Nakano, Kaku
AU  - Nakano K
FAU - Nakano, Yasuhiro
AU  - Nakano Y
FAU - Egusa, Shizuka
AU  - Egusa S
FAU - Sunagawa, Kenji
AU  - Sunagawa K
FAU - Egashira, Kensuke
AU  - Egashira K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131204
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Apolipoproteins E)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Quinolines)
RN  - 0 (Receptors, CCR2)
RN  - M5681Q5F9P (pitavastatin)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - Apolipoproteins E/genetics
MH  - Brachiocephalic Trunk/drug effects/immunology/pathology
MH  - Cell Movement/drug effects/immunology
MH  - Chemokine CCL2/antagonists & inhibitors/metabolism
MH  - Disease Models, Animal
MH  - Drug Delivery Systems/*methods
MH  - Genetic Therapy/methods
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacokinetics
MH  - Male
MH  - Mice
MH  - Mice, 129 Strain
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Monocytes/*drug effects/immunology/pathology
MH  - Nanoparticles/*metabolism/therapeutic use
MH  - Plaque, Atherosclerotic/*drug therapy/immunology/pathology
MH  - Quinolines/*pharmacokinetics
MH  - Receptors, CCR2/genetics
OTO - NOTNLM
OT  - monocytes
OT  - myocardial infarction
OT  - nanoparticles
OT  - plaque
OT  - statins, HMG-CoA
EDAT- 2013/12/07 06:00
MHDA- 2014/04/29 06:00
CRDT- 2013/12/06 06:00
PHST- 2013/12/06 06:00 [entrez]
PHST- 2013/12/07 06:00 [pubmed]
PHST- 2014/04/29 06:00 [medline]
AID - CIRCULATIONAHA.113.002870 [pii]
AID - 10.1161/CIRCULATIONAHA.113.002870 [doi]
PST - ppublish
SO  - Circulation. 2014 Feb 25;129(8):896-906. doi: 10.1161/CIRCULATIONAHA.113.002870. 
      Epub 2013 Dec 4.