Selective delivery of pitavastatin-loaded nanoparticles induces arteriogenesis upon chronic myocardial ischemia

Abstract

Recent evidence has depicted nanoparticles (NPs) targeted delivery of statin facilitates neovascularization. Herein, we aimed to examine the impact of pitavastatin carrying NPs (pitavastatin-NPs) on collateral arteries and myocardial ischemia (MI). After establishment of MI model and preparation of nanomaterials, the animals were administered pitavastatin-NPs, pitavastatin or Fluorescein isothiocyanate-NP (FITC-NP) at concentration of 0.05, 0.15 and 0.5 mg/kg through intramuscular injection. Capillary and arteriole density was measured through immunofluorescence and angiogenesis was assessed by angiography. Human endothelial cells were also treated with pitavastatin or pitavastatin-NPs, followed by detection of angiogenic activity. Pitavastatin-NPs (0.5 mg/kg) promoted endothelial cell arteriogenesis and growth of collateral arteries in the rabbit with myocardial ischemia, exerting greater efficacy than NPs, FITC-NP, or PBS. For up to 4 weeks, FITC-NPs were mainly detected in the ischemic muscle tissue. Pitavastatin-NPs induced arteriogenesis and improved exercise-induced ischemic symptoms with enhancement in angiography score. Collectively, pitavastatin-NPs enhance arteriogenesis and alleviate MI as presence of nanocarriers improve the efficacy of pitavastatin. This evidence indicates pitavastatin-NPs as a promising treatment strategy and may contribute to development of nanotechnology to promote the formation of new blood vessels.