title: Human-derived nanoparticles and vascular response to injury in rabbit carotid arteries: proof of principle.
abstract: Self-calcifying, self-replicating nanoparticles have been isolated from calcified human tissues. However, it is unclear if these nanoparticles participate in disease processes. Therefore, this study was designed to preliminarily test the hypothesis that human-derived nanoparticles are causal to arterial disease processes. One carotid artery of 3 kg male rabbits was denuded of endothelium; the contralateral artery remained unoperated as a control. Each rabbit was injected intravenously with either saline, calcified, or decalcified nanoparticles cultured from calcified human arteries or kidney stones. After 35 days, both injured and control arteries were removed for histological examination. Injured arteries from rabbits injected with saline showed minimal, eccentric intimal hyperplasia. Injured arteries from rabbits injected with calcified kidney stone- and arterial-derived nanoparticles occluded, sometimes with canalization. The calcified kidney stone-derived nanoparticles caused calcifications within the occlusion. Responses to injury in rabbits injected with decalcified kidney stone-derived nanoparticles were similar to those observed in saline-injected animals. However, decalcified arterial-derived nanoparticles produced intimal hyperplasia that varied from moderate to occlusion with canalization and calcification. This study offers the first evidence that there may be a causal relationship between human-derived nanoparticles and response to injury including calcification in arteries with damaged endothelium.
authors.affiliation: Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Maria A K
authors.initials: MA
authors.lastname: Schwartz
authors.forename: John C
authors.initials: JC
authors.lastname: Lieske
authors.forename: Vivek
authors.initials: V
authors.lastname: Kumar
authors.forename: Gerard
authors.initials: G
authors.lastname: Farell-Baril
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Miller
mesh_terms: D000818:Animals; D002114:Calcinosis / Q000139:chemically induced* / Q000473:pathology*; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology*; D002340:Carotid Artery Diseases / Q000139:chemically induced* / Q000473:pathology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D008297:Male; D053758:Nanoparticles / Q000633:toxicity*; D010865:Pilot Projects; D011817:Rabbits