Nanoparticle-mediated delivery of irbesartan induces cardioprotection from myocardial ischemia-reperfusion injury by antagonizing monocyte-mediated inflammation

Yasuhiro Nakano, Tetsuya Matoba, Masaki Tokutome, Daiki Funamoto, Shunsuke Katsuki, Gentaro Ikeda, Kazuhiro Nagaoka, Ayako Ishikita, Kaku Nakano, Jun Ichiro Koga, Kenji Sunagawa, Kensuke Egashira

Research output: Contribution to journalArticle

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Abstract

Myocardial ischemia-reperfusion (IR) injury limits the therapeutic effect of early reperfusion therapy for acute myocardial infarction (AMI), in which the recruitment of inflammatory monocytes plays a causative role. Here we develop bioabsorbable poly-lactic/glycolic acid (PLGA) nanoparticles incorporating irbesartan, an angiotensin II type 1 receptor blocker with a peroxisome proliferator-activated receptor (PPAR)γ agonistic effect (irbesartan-NP). In a mouse model of IR injury, intravenous PLGA nanoparticles distribute to the IR myocardium and monocytes in the blood and in the IR heart. Single intravenous treatment at the time of reperfusion with irbesartan-NP (3.0 mg kg -1 irbesartan), but not with control nanoparticles or irbesartan solution (3.0 mg kg -1), inhibits the recruitment of inflammatory monocytes to the IR heart, and reduces the infarct size via PPARγ-dependent anti-inflammatory mechanisms, and ameliorates left ventricular remodeling 21 days after IR. Irbesartan-NP is a novel approach to treat myocardial IR injury in patients with AMI.

Original languageEnglish
Article number29601
JournalScientific reports
Volume6
DOIs
Publication statusPublished - Jul 11 2016

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irbesartan
Myocardial Reperfusion Injury
Reperfusion Injury
Nanoparticles
Reperfusion
Myocardial Ischemia
Monocytes
glycolic acid
Inflammation
Ischemia
Peroxisome Proliferator-Activated Receptors
Myocardial Infarction
Angiotensin II Type 1 Receptor Blockers
Ventricular Remodeling
Therapeutic Uses
Secondary Prevention
Myocardium
Anti-Inflammatory Agents

All Science Journal Classification (ASJC) codes

  • General

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Nanoparticle-mediated delivery of irbesartan induces cardioprotection from myocardial ischemia-reperfusion injury by antagonizing monocyte-mediated inflammation. / Nakano, Yasuhiro; Matoba, Tetsuya; Tokutome, Masaki; Funamoto, Daiki; Katsuki, Shunsuke; Ikeda, Gentaro; Nagaoka, Kazuhiro; Ishikita, Ayako; Nakano, Kaku; Koga, Jun Ichiro; Sunagawa, Kenji; Egashira, Kensuke.

In: Scientific reports, Vol. 6, 29601, 11.07.2016.

Research output: Contribution to journalArticle

Nakano, Yasuhiro ; Matoba, Tetsuya ; Tokutome, Masaki ; Funamoto, Daiki ; Katsuki, Shunsuke ; Ikeda, Gentaro ; Nagaoka, Kazuhiro ; Ishikita, Ayako ; Nakano, Kaku ; Koga, Jun Ichiro ; Sunagawa, Kenji ; Egashira, Kensuke. / Nanoparticle-mediated delivery of irbesartan induces cardioprotection from myocardial ischemia-reperfusion injury by antagonizing monocyte-mediated inflammation. In: Scientific reports. 2016 ; Vol. 6.
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