title: Anti-atherogenic effect of trivalent chromium-loaded CPMV nanoparticles in human aortic smooth muscle cells under hyperglycemic conditions in vitro.
abstract: 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-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.
authors.affiliation: Department of Integrative Medical Sciences, Northeast Ohio Medical University, 4209 State Route 44, Rootstown, OH 44272-0095, USA. praman@neomed.edu and School of Biomedical Sciences, Kent State University, Kent, OH, USA.
authors.forename: Rituparna
authors.initials: R
authors.lastname: Ganguly
authors.affiliation: Department of Biomedical Engineering, 10990 Euclid Avenue and Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Wen
authors.affiliation: Department of Integrative Medical Sciences, Northeast Ohio Medical University, 4209 State Route 44, Rootstown, OH 44272-0095, USA. praman@neomed.edu.
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Myer
authors.affiliation: Department of Integrative Medical Sciences, Northeast Ohio Medical University, 4209 State Route 44, Rootstown, OH 44272-0095, USA. praman@neomed.edu.
authors.forename: Tori
authors.initials: T
authors.lastname: Czech
authors.affiliation: Department of Integrative Medical Sciences, Northeast Ohio Medical University, 4209 State Route 44, Rootstown, OH 44272-0095, USA. praman@neomed.edu and School of Biomedical Sciences, Kent State University, Kent, OH, USA.
authors.forename: Soumyadip
authors.initials: S
authors.lastname: Sahu
authors.affiliation: Department of Biomedical Engineering, 10990 Euclid Avenue and Case Western Reserve University, Cleveland, OH, USA and Department of Radiology, 10990 Euclid Avenue and Case Western Reserve University, Cleveland, OH, USA and Department of Materials Science and Engineering, 10990 Euclid Avenue and Case Western Reserve University, Cleveland, OH, USA and Department of Macromolecular Science and Engineering, 10990 Euclid Avenue and Case Western Reserve University, Cleveland, OH, USA and Case Comprehensive Cancer Center, 10990 Euclid Avenue and Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Steinmetz
authors.affiliation: Department of Integrative Medical Sciences, Northeast Ohio Medical University, 4209 State Route 44, Rootstown, OH 44272-0095, USA. praman@neomed.edu and School of Biomedical Sciences, Kent State University, Kent, OH, USA.
authors.forename: Priya
authors.initials: P
authors.lastname: Raman
mesh_terms: D001011:Aorta / Q000378:metabolism*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000628:therapy; D001391:Azo Compounds / Q000737:chemistry; D049109:Cell Proliferation; D002478:Cells, Cultured; D002712:Chlorides / Q000737:chemistry*; D017608:Chromium Compounds / Q000737:chemistry*; D017798:Comovirus; D016207:Cytokines / Q000378:metabolism; D016503:Drug Delivery Systems; D005947:Glucose / Q000737:chemistry; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry; D018809:Proliferating Cell Nuclear Antigen / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D001391:Azo Compounds; D002712:Chlorides; D017608:Chromium Compounds; D016207:Cytokines; D008055:Lipids; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D016212:Transforming Growth Factor beta; C017133:chromous chloride; C011049:oil red O; D005947:Glucose; C022990:chromic chloride