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Effects of nanoparticle-mediated delivery of pitavastatin on atherosclerotic plaques in ApoE-knockout mice and THP-1-derived macrophages

机译:纳米介导的匹伐他汀递送对ApoE基因敲除小鼠和THP-1衍生的巨噬细胞中动脉粥样硬化斑块的影响

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摘要

The treatment of atherosclerosis remains complex. Pitavastatin serves an important role in the prevention and treatment of atherosclerosis. The present study aimed to investigate the effects of nanoparticle (NP)-mediated delivery of pitavastatin into atherosclerotic plaques as a novel treatment method for atherosclerosis. The results of the present study demonstrated that pitavastatin-NP was more effective in attenuating the size of atherosclerotic plaques and enhancing the stability of plaques compared with pitavastatin alone. In an apolipoprotein E (ApoE)-knockout mouse model of atherosclerosis, a single intravenous injection of fluorescein isothiocyanate-NP resulted in the delivery of NP into atherosclerotic plaques for up to 7 days post-injection. In ApoE-knockout mice and THP-1-derived macrophages, pitavastatin-NP attenuated the development of atherosclerosis, which was associated with regulating lipid metabolism, and inhibited the secretion of inflammatory markers compared with pitavastatin alone. Additionally, the treatment advantages of pitavastatin-NP were independent of lipid lowering. The results demonstrated that pitavastatin-NP administration was more effective in attenuating the development of atherosclerotic plaques compared with systemic administration of pitavastatin.
机译:动脉粥样硬化的治疗仍然很复杂。匹伐他汀在预防和治疗动脉粥样硬化中起重要作用。本研究旨在研究纳米颗粒(NP)介导的匹伐他汀向动脉粥样硬化斑块中递送的作用,作为动脉粥样硬化的一种新型治疗方法。本研究的结果表明,与单独使用匹伐他汀相比,匹伐他汀-NP在减轻动脉粥样硬化斑块的大小和增强斑块的稳定性方面更有效。在动脉粥样硬化的载脂蛋白E(ApoE)敲除小鼠模型中,单次静脉内注射异硫氰酸荧光素-NP导致NP在注射后长达7天的时间内被递送到动脉粥样硬化斑块中。与单独使用匹伐他汀相比,在ApoE敲除小鼠和THP-1衍生的巨噬细胞中,匹伐他汀-NP减轻了动脉粥样硬化的发展,这与调节脂质代谢有关,并抑制了炎性标志物的分泌。此外,匹伐他汀-NP的治疗优势与脂质降低无关。结果表明,与全身给药匹伐他汀相比,匹伐他汀-NP给药在减轻动脉粥样硬化斑块的发展方面更有效。

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