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- W2508275087 abstract "Introduction: Pulmonary arterial hypertension (PAH) is an intractable disease of small pulmonary artery (PA) in which multiple pathogenetic factors are involved. Statins have anti-inflammatory and anti-proliferative effects and may have beneficial effect on PAH. We developed a novel nanoparticle (NP)-mediated drug delivery system to target statins into small PAs in the PAH lung. Methods and Results: SD rats were injected 60 mg/kg of MCT. On day 17, they were randomly assigned to the following 5 groups; daily intravenous administration of 1) vehicle, 2) FITC-NP, 3) pitavastatin (1, 3, 10 or 30 mg/kg), or 4) pitavastatin-NP (containing 1 or 3 mg/kg pitavastatin), or 5) oral sildenafil (10 mg/kg/day). Intravenous administration of FITC-NP showed marked delivery of NP into SMA-positive PAs. Compared with pitavastatin alone, treatment with pitavastatin-NP attenuated the progression of PAH in lower dose on day 21. This was associated with reduction of inflammation in the lung and remodeling of small PAs. Pitavastatin-NP had no vasodilatory effects. In contrast, oral sildenafil acutely lowered PA pressure and attenuated the progression of PAH equivalent to pitavastatin-NP on day 21. Interestingly, sildenafil had no effect on inflammation and small PA remodeling. In separate experiments, only treatment with pitavastatin-NP reduced the mortality rate at day 35. Conclusions: Pitavastatin-NP can be a novel therapeutic modality for PAH and phase IIa clinical trial is under contemplation." @default.
- W2508275087 created "2016-09-16" @default.
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- W2508275087 date "2016-09-01" @default.
- W2508275087 modified "2023-09-27" @default.
- W2508275087 title "Nanoparticle-Mediated Targeting of Pitavastatin into Small Pulmonary Arteries by Intravenous Administration Attenuates the Progression of Monocrotaline-Induced Pulmonary Hypertension in Rats" @default.
- W2508275087 doi "https://doi.org/10.1016/j.cardfail.2016.07.248" @default.
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