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Am J Physiol Heart Circ Physiol 296: H1434-H1441, 2009. First published March 13, 2009; doi:10.1152/ajpheart.00993.2008
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Systemic injection of planktonic forms of mammalian-derived nanoparticles alters arterial response to injury in rabbits

Maria K Schwartz,1 John C Lieske,2 Larry W. Hunter,3 and Virginia M Miller1,3

1Department of Physiology and Biomedical Engineering, 2Division of Nephrology, Department of Internal Medicine, and 3Department of Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota

Submitted 12 September 2008 ; accepted in final form 6 March 2009

Experiments were designed to test the hypothesis that the systemic delivery of planktonic forms of nanoparticles (NPs) derived from calcified, diseased human tissue or bovine blood are transmissible particles that exacerbate arterial response to injury. New Zealand White rabbits in which the endothelium was mechanically removed from one carotid artery were injected intravenously with either saline (control), lipopolysaccharide (LPS; surrogate for subclinical infection), hydroxyapatite crystals (HA; surrogate for NP shell), HA crystals exposed to culture media, or planktonic forms of bovine- or human-derived NPs. Carotid arteries were monitored by ultrasonography for 5 wk and then removed for histological examination. Uninjured arteries from all animals in each group remained patent with a normal anatomy. Injured arteries from 6 of 11 animals injected with human-derived NPs occluded and/or calcified; none of the injured arteries from animals in the other groups occluded (n = 28; P ≤ 0.05). Injured arteries of rabbits injected with LPS or HA crystals developed eccentric hyperplasia. Discontinuous internal elastic laminae and thinning media characterized arteries from animals injected with bovine-derived NPs or cultured HA crystals. In conclusion, the systemic administration of planktonic forms of human-derived NPs exacerbated arterial response to injury distinct from that of bovine-derived NPs and other inflammatory agents.

inflammation; intimal hyperplasia; carotid artery



Address for reprint requests and other correspondence: V. M. Miller, Medical Sciences 4-62, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905 (e-mail: miller.virginia{at}mayo.edu)







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