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

Int Heart J. 2017 Aug 3;58(4):615-623. doi: 10.1536/ihj.16-457. Epub 2017 Jul 13.

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.

Keywords: Angiotensin II; Poly (lactic-co-glicdic acid); Statin.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Drug Delivery Systems*
  • Heart Failure / etiology
  • Heart Failure / physiopathology
  • Heart Failure / prevention & control*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Inflammation / drug therapy*
  • Injections, Intravenous
  • Macrophages
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Monocytes
  • Myocardial Infarction / complications
  • Myocardial Infarction / physiopathology*
  • Nanoparticles / administration & dosage*
  • Quinolines / administration & dosage*
  • Ventricular Remodeling / drug effects*

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Quinolines
  • pitavastatin