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.

Ganguly Rituparna; Wen Amy M; Myer Ashley B; Czech Tori; Sahu Soumyadip; Steinmetz Nicole F; Raman Priya

Nanoscale

2016

2016-03

Atherosclerosis, a major macrovascular complication associated with diabetes, poses a tremendous burden on national health care expenditure. Despite extensive efforts, cost-effective remedies are unknown. Therapies for atherosclerosis are challenged by a lack of targeted drug delivery approaches. 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 2000 drug molecules per particle. Using immunofluorescence microscopy, we show that CPMV-Cr is readily taken up 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 by attenuation in high glucose-induced phospho-p38 and pAkt expression. Moreover, CPMV-Cr inhibits the expression of pro-inflammatory cytokines, transforming growth factor-beta (TGF-beta) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), 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.

*Comovirus; Aorta/*metabolism; Atherosclerosis/*drug therapy/therapy; Azo Compounds/chemistry; Cell Proliferation; Cells; Chlorides/*chemistry; Chromium Compounds/*chemistry; Cultured; Cytokines/metabolism; Drug Delivery Systems; Electron; Fluorescence; Glucose/chemistry; Humans; Hyperglycemia/*metabolism; Lipids/chemistry; Microscopy; Myocytes; Nanoparticles/chemistry; NF-kappa B/metabolism; Proliferating Cell Nuclear Antigen/chemistry; Smooth Muscle/*metabolism; Spectrophotometry; Transforming Growth Factor beta/metabolism; Transmission; Ultraviolet

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