Abstract

Our group has isolated and propagated self-replicating, self-calcifying nanoparticles (NPs) from diseased human kidney stones and atherosclerotic aneurysms. To demonstrate that these biologic NPs can transmit disease to naive animals, adult male rabbits were inoculated intravenously with either a single dose of biologic NPs derived from human calcified aneurysms, diluent (control), or E. coli derived LPS (control for endotoxin-induced inflammation). Animals were pretreated by endothelial denudation of one carotid artery. Only endothelium-denuded carotid arteries of animals injected with NPs were occluded with myointimal hyperplasia and focal calcification when examined by light microscopy 35 days after injury. In contrast, denuded arteries of animals treated with diluent demonstrated only minor eccentric myointimal hyperplasia, while concentric myointimal hyperplasia (without calcification) was observed in the rabbit treated with LPS. Therefore, biologic calcified NPs localize to areas of arterial injury and invoke a proliferative response that includes calcification. These results suggest that NPs potentially represent a previously unrecognized pathogenic co-factor for atherosclerotic and calcific arterial disease. (Supported by grants from Nanobac Pharmaceuticals, Inc. and the Mayo Fnd.)

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