Nanoparticle-Mediated Delivery of Irbesartan Induces Cardioprotection from Myocardial Ischemia-Reperfusion Injury by Antagonizing Monocyte-Mediated Inflammation.
Nanoparticle-Mediated Delivery of Irbesartan Induces Cardioprotection from Myocardial Ischemia-Reperfusion Injury by Antagonizing Monocyte-Mediated Inflammation.
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DOI：
10.1038/srep29601
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发表时间：
2016-07-11
影响因子：
4.6
通讯作者：
Egashira K
中科院分区：
文献类型：
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作者：
Nakano Y;Matoba T;Tokutome M;Funamoto D;Katsuki S;Ikeda G;Nagaoka K;Ishikita A;Nakano K;Koga J;Sunagawa K;Egashira K
心肌缺血再灌注损伤限制了急性心肌梗死（AMI）早期再灌注治疗的疗效，其中炎性单核细胞的募集起着致病作用。在这里，我们开发了可生物吸收的聚乳酸/乙醇酸（PLGA）纳米粒，其中包含厄贝沙坦，一种具有过氧化物酶体增殖物激活受体（PPAR）γ激动作用的血管紧张素II 1型受体阻滞剂（厄贝沙坦-NP）。在IR损伤的小鼠模型中，静脉内PLGA纳米颗粒分布到血液和IR心脏中的IR心肌和单核细胞。再灌注时单次静脉注射厄贝沙坦-NP（3.0 mg kg−1厄贝沙坦），但不使用对照纳米颗粒或厄贝沙坦溶液（3.0 mg kg−1），抑制炎性单核细胞向IR心脏的募集，并通过PPARγ依赖性抗炎机制减少梗死面积，Irbesartan-NP可改善IR后21天的左室重构，是治疗AMI患者心肌IR损伤的一种新方法。
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.