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.
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