PMID- 33455994
OWN - NLM
STAT- MEDLINE
DCOM- 20220309
LR  - 20220329
IS  - 1880-3873 (Electronic)
IS  - 1340-3478 (Print)
IS  - 1340-3478 (Linking)
VI  - 29
IP  - 1
DP  - 2022 Jan 1
TI  - Nanoparticle-Mediated Delivery of Pitavastatin to Monocytes/Macrophages Inhibits 
      Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Apoe(-/-) Mice.
PG  - 111-125
LID - 10.5551/jat.54379 [doi]
AB  - AIM: Abdominal aortic aneurysm (AAA) is a lethal and multifactorial disease. To 
      prevent a rupture and dissection of enlarged AAA, prophylactic surgery and 
      stenting are currently available. There are, however, no medical therapies 
      preventing these complications of AAA. Statin is one of the candidates, but its 
      efficacy on AAA formation/progression remains controversial. We have previously 
      demonstrated that nanoparticles (NPs) incorporating pitavastatin 
      (Pitava-NPs)-clinical trials using these nanoparticles have been already 
      conducted-suppressed progression of atherosclerosis in apolipoprotein E-deficient 
      ( Apoe(-/-)) mice. Therefore, we have tested a hypothesis that 
      monocytes/macrophages-targeting delivery of pitavastatin prevents the progression 
      of AAA. METHODS: Angiotensin II was intraperitoneally injected by osmotic 
      mini-pumps to induce AAA formation in Apoe(-/-) mice. NPs consisting of 
      poly(lactic-co-glycolic acid) were used for in vivo delivery of pitavastatin to 
      monocytes/macrophages. RESULTS: Intravenously administered Pitava-NPs (containing 
      0.012 mg/kg/week pitavastatin) inhibited AAA formation accompanied with reduction 
      of macrophage accumulation and monocyte chemoattractant protein-1 (MCP-1) 
      expression. Ex vivo molecular imaging revealed that Pitava-NPs not only reduced 
      macrophage accumulation but also attenuated matrix metalloproteinase activity in 
      the abdominal aorta, which was underpinned by attenuated elastin degradation. 
      CONCLUSION: These results suggest that Pitava-NPs inhibit AAA formation 
      associated with reduced macrophage accumulation and MCP-1 expression. This 
      clinically feasible nanomedicine could be an innovative therapeutic strategy that 
      prevents devastating complications of AAA.
FAU - Katsuki, Shunsuke
AU  - Katsuki S
AD  - The Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 
      Kyushu University.
FAU - Koga, Jun-Ichiro
AU  - Koga JI
AD  - The Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 
      Kyushu University.
FAU - Matoba, Tetsuya
AU  - Matoba T
AD  - The Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 
      Kyushu University.
FAU - Umezu, Ryuta
AU  - Umezu R
AD  - The Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 
      Kyushu University.
FAU - Nakashiro, Soichi
AU  - Nakashiro S
AD  - The Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 
      Kyushu University.
FAU - Nakano, Kaku
AU  - Nakano K
AD  - The Department of Cardiovascular Research, Development, and Translational 
      Medicine, Center for Disruptive Cardiovascular Innovation, Kyushu University.
FAU - Tsutsui, Hiroyuki
AU  - Tsutsui H
AD  - The Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 
      Kyushu University.
FAU - Egashira, Kensuke
AU  - Egashira K
AD  - The Department of Cardiovascular Research, Development, and Translational 
      Medicine, Center for Disruptive Cardiovascular Innovation, Kyushu University.
AD  - The Department of Translational Medicine, Kyushu University Graduate School of 
      Pharmaceutical Sciences.
LA  - eng
PT  - Journal Article
DEP - 20210123
PL  - Japan
TA  - J Atheroscler Thromb
JT  - Journal of atherosclerosis and thrombosis
JID - 9506298
RN  - 0 (Apolipoproteins E)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Quinolines)
RN  - 11128-99-7 (Angiotensin II)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - M5681Q5F9P (pitavastatin)
SB  - IM
MH  - Angiotensin II
MH  - Animals
MH  - Aortic Aneurysm, Abdominal/blood/pathology/*prevention & control
MH  - Apolipoproteins E
MH  - Chemokine CCL2/blood
MH  - Disease Models, Animal
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*administration & dosage
MH  - Macrophages/*drug effects
MH  - Male
MH  - Matrix Metalloproteinases/blood
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Monocytes/*drug effects
MH  - *Nanoparticles
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Quinolines/*administration & dosage
PMC - PMC8737070
OTO - NOTNLM
OT  - Aneurysm
OT  - Inflammation
OT  - Monocyte
OT  - Nanoparticle
OT  - Statins
EDAT- 2021/01/19 06:00
MHDA- 2022/03/11 06:00
PMCR- 2022/01/01
CRDT- 2021/01/18 05:27
PHST- 2021/01/19 06:00 [pubmed]
PHST- 2022/03/11 06:00 [medline]
PHST- 2021/01/18 05:27 [entrez]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.5551/jat.54379 [doi]
PST - ppublish
SO  - J Atheroscler Thromb. 2022 Jan 1;29(1):111-125. doi: 10.5551/jat.54379. Epub 2021 
      Jan 23.