Nanoparticle-Mediated Delivery of Pitavastatin to Monocytes/Macrophages Inhibits Left Ventricular Remodeling After Acute Myocardial Infarction by Inhibiting Monocyte-Mediated Inflammation

• Mao Yajing

  Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University

• Koga Jun-ichiro

  Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University Department of Cardiovascular Research, Development, and Translational Medicine, Center for Disruptive Cardiovascular Medicine, Kyushu University

• Tokutome Masaki

  Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University

• Matoba Tetsuya

  Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University

• Ikeda Gentaro

  Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University Department of Cardiovascular Research, Development, and Translational Medicine, Center for Disruptive Cardiovascular Medicine, Kyushu University

• Nakano Kaku

  Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University Department of Cardiovascular Research, Development, and Translational Medicine, Center for Disruptive Cardiovascular Medicine, Kyushu University

• Egashira Kensuke

  Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University Department of Cardiovascular Research, Development, and Translational Medicine, Center for Disruptive Cardiovascular Medicine, Kyushu University

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.

Journal

• International Heart Journal

  International Heart Journal 58 (4), 615-623, 2017

  International Heart Journal Association

Keywords

• Angiotensin II
• Statin
• Poly (lactic-co-glicdic acid)

Details

• CRID: 1390282680201702272
• NII Article ID: 130005901270
• DOI: 10.1536/ihj.16-457
• ISSN: 13493299
• ISSN: 13492365
• PubMed: 28701679
• Web Site: https://www.jstage.jst.go.jp/article/ihj/58/4/58_16-457/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2018093181
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed