Anti-atherogenic effect of trivalent chromium-loaded CPMV nanoparticles in human aortic smooth muscle cells under hyperglycemic conditions in vitro.
Anti-atherogenic effect of trivalent chromium-loaded CPMV nanoparticles in human aortic smooth muscle cells under hyperglycemic conditions in vitro.
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DOI：
10.1039/c6nr00398b
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发表时间：
2016-03-28
期刊：
影响因子：
6.7
通讯作者：
Raman P
中科院分区：
文献类型：
--
作者：
Ganguly R;Wen AM;Myer AB;Czech T;Sahu S;Steinmetz NF;Raman P
动脉粥样硬化是糖尿病的主要大血管并发症，给国家卫生保健支出带来巨大负担。尽管作出了广泛的努力，但尚不知道有哪些成本效益高的补救办法。动脉粥样硬化的治疗受到缺乏靶向药物递送方法的挑战。为了实现这一目标，我们转向利用植物病毒豇豆花叶病毒（CPMV）形成的纳米颗粒的生物衍生药物递送系统。本文的目的是研究在高血糖条件下在人主动脉平滑肌细胞（HASMC）中负载有益的矿物质营养物三价铬的CPMV纳米颗粒的抗动脉粥样硬化潜力。建立了非共价加载方案，得到每个颗粒携带2，000个药物的CrCl 3加载的CPMV（CPMV-Cr）。使用免疫荧光显微镜，我们表明，CPMV-Cr是很容易吸收的HASMC在体外。在葡萄糖（25 mM）刺激的细胞中，100 nM CPMV-Cr抑制HASMC增殖，同时减弱增殖细胞核抗原（PCNA，增殖标志物）表达。这伴随着高葡萄糖诱导的磷酸化p38和pAkt表达的减弱。此外，CPMV-Cr抑制葡萄糖刺激的HASMCs中促炎细胞因子、转化生长因子-β（TGF-β）和活化B细胞的核因子κ轻链增强子（NF-κB）的表达。最后，葡萄糖刺激的脂质摄取显着废除CPMV-Cr，油红O染色显示。总之，这些数据提供了关键的细胞证据CPMV-Cr在血管平滑肌细胞（VSMC）在高血糖条件下，可能会促进糖尿病动脉粥样硬化的新的治疗风险的动脉粥样硬化保护作用。新型三价铬负载豇豆花叶病毒纳米颗粒在糖尿病环境中的血管平滑肌细胞中表现出动脉粥样硬化保护作用。
Atherosclerosis, a major macrovascular complication associated with diabetes, poses tremendous burden on national health care expenditure. Despite extensive efforts, cost-effective remedies are unknown. Therapies for atherosclerosis are challenged by lack of targeted drug delivery approach. Toward this goal, we turn to a biology-derived drug delivery system utilizing nanoparticles formed by the plant virus, Cowpea mosaic virus (CPMV). The aim herein is to investigate the anti-atherogenic potential of the beneficial mineral nutrient, trivalent chromium, loaded CPMV nanoparticles in human aortic smooth muscle cells (HASMC) under hyperglycemic conditions. A non-covalent loading protocol is established yielding CrCl3-loaded CPMV (CPMV-Cr) carrying 2,000 drugs per particle. Using immunofluorescence microscopy, we show that CPMV-Cr is readily uptaken by HASMC in vitro. In glucose (25 mM)-stimulated cells, 100 nM CPMV-Cr inhibits HASMC proliferation concomitant to attenuated proliferating cell nuclear antigen (PCNA, proliferation marker) expression. This is accompanied with attenuation in high glucose-induced phospho-p38 and pAkt expression. Moreover, CPMV-Cr inhibits expression of pro-inflammatory cytokines, transforming growth factor-β (TGF-β) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), in glucose-stimulated HASMCs. Finally glucose-stimulated lipid uptake is remarkably abrogated by CPMV-Cr, revealed by Oil Red O staining. Together, these data provide key cellular evidence for an atheroprotective effect of CPMV-Cr in vascular smooth muscle cells (VSMC) under hyperglycemic conditions that may promote novel therapeutic ventures for diabetic atherosclerosis. Novel trivalent chromium-loaded cowpea mosaic virus nanoparticles exhibit atheroprotective effect in vascular smooth muscle cells in a diabetic milieu.
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影响因子：
16.2
作者：
Isomaa, B;Almgren, P;Groop, L
通讯作者：
Groop, L
DOI：
10.1007/978-1-62703-751-8_16
发表时间：
2014-01-01
期刊：
VIRUS HYBRIDS AS NANOMATERIALS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Cho, Choi-Fong;Shukla, Sourabh;Lewis, John D.
通讯作者：
Lewis, John D.
影响因子：
37.8
作者：
Haffner, SM;Mykkänen, L;Stern, MP
通讯作者：
Stern, MP
影响因子：
15.9
作者：
Bornstein, P
通讯作者：
Bornstein, P
影响因子：
2.2
作者：
Jain, SK;Lim, G
通讯作者：
Lim, G