Nanoparticle-mediated delivery of pitavastatin to monocytes/macrophages inhibits left ventricular remodeling after acute myocardial infarction by inhibiting monocyte-mediated inflammation

Yajing Mao, Jun Ichiro Koga, Masaki Tokutome, Tetsuya Matoba, Gentaro Ikeda, Kaku Nakano, Kensuke Egashira

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Left ventricular (LV) remodeling after myocardial infarction (MI) causes heart failure. Although medical therapies including angiotensin converting enzyme inhibitors show inhibitory effects on post-infarct LV remodeling, the prognosis of patients with post-infarct heart failure is still poor. Accumulating evidence suggests that an inflammatory response is implicated in the process of post-infarct LV remodeling. Therefore, we hypothesized that anti-inflammatory therapy by nanoparticle-mediated monocyte/macrophage-targeting delivery of pitavastatin may protect the heart from post-infarct LV remodeling. Male C57BL/6 mice were subjected to permanent coronary ligation and pitavastatin-incorporating nanoparticles (Pitavastatin-NPs) were intravenously injected for 3 to 5 consecutive days. Pitavastatin-NPs were delivered to CD11b+ monocytes/macrophages, but not to cardiomyocytes. Treatment with Pitavastatin-NPs after establishment of MI attenuated post-infarct LV remodeling accompanied by a reduction of monocytes/macrophages in the heart, whereas pitavastatin solution treatment did not. Pitavastatin-NPs inhibited mobilization of monocytes from the spleen after MI. In mice after splenectomy, Pitavastatin-NPs still decreased the number of monocytes/macrophages in the infarcted heart and inhibited post-infarct LV remodeling. Nanoparticle-mediated delivery of pitavastatin to monocytes/macrophages may be a novel therapeutic strategy to protect the heart from post-infarct LV remodeling. Inhibition of monocyte mobilization from the bone marrow is one of the major mechanisms by which Pitavastatin-NPs attenuated post-infarct LV remodeling.

Original languageEnglish
Pages (from-to)615-623
Number of pages9
JournalInternational heart journal
Volume58
Issue number4
DOIs
Publication statusPublished - Aug 2 2017

Fingerprint

Ventricular Remodeling
Nanoparticles
Monocytes
Macrophages
Myocardial Infarction
Inflammation
Heart Failure
Therapeutics
pitavastatin
Splenectomy
Inbred C57BL Mouse
Angiotensin-Converting Enzyme Inhibitors
Cardiac Myocytes
Ligation
Anti-Inflammatory Agents
Spleen
Bone Marrow

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Nanoparticle-mediated delivery of pitavastatin to monocytes/macrophages inhibits left ventricular remodeling after acute myocardial infarction by inhibiting monocyte-mediated inflammation. / Mao, Yajing; Koga, Jun Ichiro; Tokutome, Masaki; Matoba, Tetsuya; Ikeda, Gentaro; Nakano, Kaku; Egashira, Kensuke.

In: International heart journal, Vol. 58, No. 4, 02.08.2017, p. 615-623.

Research output: Contribution to journalArticle

@article{fa7e79a347854f068abfd0cc10649ab8,
title = "Nanoparticle-mediated delivery of pitavastatin to monocytes/macrophages inhibits left ventricular remodeling after acute myocardial infarction by inhibiting monocyte-mediated inflammation",
abstract = "Left ventricular (LV) remodeling after myocardial infarction (MI) causes heart failure. Although medical therapies including angiotensin converting enzyme inhibitors show inhibitory effects on post-infarct LV remodeling, the prognosis of patients with post-infarct heart failure is still poor. Accumulating evidence suggests that an inflammatory response is implicated in the process of post-infarct LV remodeling. Therefore, we hypothesized that anti-inflammatory therapy by nanoparticle-mediated monocyte/macrophage-targeting delivery of pitavastatin may protect the heart from post-infarct LV remodeling. Male C57BL/6 mice were subjected to permanent coronary ligation and pitavastatin-incorporating nanoparticles (Pitavastatin-NPs) were intravenously injected for 3 to 5 consecutive days. Pitavastatin-NPs were delivered to CD11b+ monocytes/macrophages, but not to cardiomyocytes. Treatment with Pitavastatin-NPs after establishment of MI attenuated post-infarct LV remodeling accompanied by a reduction of monocytes/macrophages in the heart, whereas pitavastatin solution treatment did not. Pitavastatin-NPs inhibited mobilization of monocytes from the spleen after MI. In mice after splenectomy, Pitavastatin-NPs still decreased the number of monocytes/macrophages in the infarcted heart and inhibited post-infarct LV remodeling. Nanoparticle-mediated delivery of pitavastatin to monocytes/macrophages may be a novel therapeutic strategy to protect the heart from post-infarct LV remodeling. Inhibition of monocyte mobilization from the bone marrow is one of the major mechanisms by which Pitavastatin-NPs attenuated post-infarct LV remodeling.",
author = "Yajing Mao and Koga, {Jun Ichiro} and Masaki Tokutome and Tetsuya Matoba and Gentaro Ikeda and Kaku Nakano and Kensuke Egashira",
year = "2017",
month = "8",
day = "2",
doi = "10.1536/ihj.16-457",
language = "English",
volume = "58",
pages = "615--623",
journal = "International Heart Journal",
issn = "1349-2365",
publisher = "International Heart Journal Association",
number = "4",

}

TY - JOUR

T1 - Nanoparticle-mediated delivery of pitavastatin to monocytes/macrophages inhibits left ventricular remodeling after acute myocardial infarction by inhibiting monocyte-mediated inflammation

AU - Mao, Yajing

AU - Koga, Jun Ichiro

AU - Tokutome, Masaki

AU - Matoba, Tetsuya

AU - Ikeda, Gentaro

AU - Nakano, Kaku

AU - Egashira, Kensuke

PY - 2017/8/2

Y1 - 2017/8/2

N2 - Left ventricular (LV) remodeling after myocardial infarction (MI) causes heart failure. Although medical therapies including angiotensin converting enzyme inhibitors show inhibitory effects on post-infarct LV remodeling, the prognosis of patients with post-infarct heart failure is still poor. Accumulating evidence suggests that an inflammatory response is implicated in the process of post-infarct LV remodeling. Therefore, we hypothesized that anti-inflammatory therapy by nanoparticle-mediated monocyte/macrophage-targeting delivery of pitavastatin may protect the heart from post-infarct LV remodeling. Male C57BL/6 mice were subjected to permanent coronary ligation and pitavastatin-incorporating nanoparticles (Pitavastatin-NPs) were intravenously injected for 3 to 5 consecutive days. Pitavastatin-NPs were delivered to CD11b+ monocytes/macrophages, but not to cardiomyocytes. Treatment with Pitavastatin-NPs after establishment of MI attenuated post-infarct LV remodeling accompanied by a reduction of monocytes/macrophages in the heart, whereas pitavastatin solution treatment did not. Pitavastatin-NPs inhibited mobilization of monocytes from the spleen after MI. In mice after splenectomy, Pitavastatin-NPs still decreased the number of monocytes/macrophages in the infarcted heart and inhibited post-infarct LV remodeling. Nanoparticle-mediated delivery of pitavastatin to monocytes/macrophages may be a novel therapeutic strategy to protect the heart from post-infarct LV remodeling. Inhibition of monocyte mobilization from the bone marrow is one of the major mechanisms by which Pitavastatin-NPs attenuated post-infarct LV remodeling.

AB - Left ventricular (LV) remodeling after myocardial infarction (MI) causes heart failure. Although medical therapies including angiotensin converting enzyme inhibitors show inhibitory effects on post-infarct LV remodeling, the prognosis of patients with post-infarct heart failure is still poor. Accumulating evidence suggests that an inflammatory response is implicated in the process of post-infarct LV remodeling. Therefore, we hypothesized that anti-inflammatory therapy by nanoparticle-mediated monocyte/macrophage-targeting delivery of pitavastatin may protect the heart from post-infarct LV remodeling. Male C57BL/6 mice were subjected to permanent coronary ligation and pitavastatin-incorporating nanoparticles (Pitavastatin-NPs) were intravenously injected for 3 to 5 consecutive days. Pitavastatin-NPs were delivered to CD11b+ monocytes/macrophages, but not to cardiomyocytes. Treatment with Pitavastatin-NPs after establishment of MI attenuated post-infarct LV remodeling accompanied by a reduction of monocytes/macrophages in the heart, whereas pitavastatin solution treatment did not. Pitavastatin-NPs inhibited mobilization of monocytes from the spleen after MI. In mice after splenectomy, Pitavastatin-NPs still decreased the number of monocytes/macrophages in the infarcted heart and inhibited post-infarct LV remodeling. Nanoparticle-mediated delivery of pitavastatin to monocytes/macrophages may be a novel therapeutic strategy to protect the heart from post-infarct LV remodeling. Inhibition of monocyte mobilization from the bone marrow is one of the major mechanisms by which Pitavastatin-NPs attenuated post-infarct LV remodeling.

UR - http://www.scopus.com/inward/record.url?scp=85026804750&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85026804750&partnerID=8YFLogxK

U2 - 10.1536/ihj.16-457

DO - 10.1536/ihj.16-457

M3 - Article

C2 - 28701679

AN - SCOPUS:85026804750

VL - 58

SP - 615

EP - 623

JO - International Heart Journal

JF - International Heart Journal

SN - 1349-2365

IS - 4

ER -