4.4 Article

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

Journal

EXPERIMENTAL AND THERAPEUTIC MEDICINE
Volume 19, Issue 6, Pages 3787-3797

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/etm.2020.8632

Keywords

atherosclerosis; nanotechnology; pitavastatin; macrophage; lipid metabolism

Funding

  1. Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education [KF201306]
  2. National Natural Science Foundation of China [81200083, 81300038]
  3. [2013020200-206]

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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 in vitro 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.

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