title: Nanoparticle-Mediated Delivery of Irbesartan Induces Cardioprotection from Myocardial Ischemia-Reperfusion Injury by Antagonizing Monocyte-Mediated Inflammation.
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.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakano
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matoba
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Tokutome
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Funamoto
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Katsuki
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Gentaro
authors.initials: G
authors.lastname: Ikeda
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nagaoka
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Ishikita
authors.affiliation: Department of Cardiovascular Research, Development, and Translational Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Kaku
authors.initials: K
authors.lastname: Nakano
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Jun-Ichiro
authors.initials: J
authors.lastname: Koga
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.|Department of Cardiovascular Research, Development, and Translational Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Egashira
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage*; D000077405:Irbesartan; D019344:Lactic Acid / Q000008:administration & dosage; D051379:Mice; D009000:Monocytes / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000150:complications*; D009205:Myocarditis / Q000517:prevention & control; D053758:Nanoparticles / Q000008:administration & dosage*; D011100:Polyglycolic Acid / Q000008:administration & dosage; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D015427:Reperfusion Injury / Q000517:prevention & control*; D013777:Tetrazoles / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D001713:Biphenyl Compounds; D002316:Cardiotonic Agents; D004337:Drug Carriers; D013777:Tetrazoles; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000077405:Irbesartan