Biologic nanoparticles and platelet reactivity.
OBJECTIVE
Nanosized particles (NPs) enriched in hydroxyapatite and protein isolated from calcified human tissue accelerate occlusion of endothelium-denuded arteries when injected intravenously into rabbits. Since platelet aggregation and secretory processes participate in normal hemostasis, thrombosis and vascular remodeling, experiments were designed to determine if these biologic NPs alter specific platelet functions in vitro.


METHODS
Platelet-rich plasma was prepared from citrate anticoagulated human blood. Platelet aggregation and ATP secretion were monitored in response to thrombin receptor agonists peptide (10 microM) or convulxin (50 microg/ml) prior to and following 15 min incubation with either control solution, human-derived NPs, bovine-derived NPs or crystals of hydroxyapatite at concentrations of 50 and 150 nephelometric turbidity units.


RESULTS
Incubation of platelets for 15 min with either human- or bovine-derived NPs reduced aggregation induced by thrombin receptor activator peptide and convulxin in a concentration-dependent manner. Hydroxyapatite caused a greater inhibition than either of the biologically derived NPs. Human-derived NPs increased ATP secretion by unstimulated platelets during the 15 min incubation period.


CONCLUSIONS
Effects of bovine-derived and hydroxyapatite NPs on basal release of ATP were both time and concentration dependent. These results suggest that biologic NPs modulate both platelet aggregation and secretion. Biologically derived NPs could modify platelet responses within the vasculature, thereby reducing blood coagulability and the vascular response to injury.
Department of Surgery, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA. miller.virginia@mayo.edu
Virginia M
VM
Miller
Larry W
LW
Hunter
Kevin
K
Chu
Vivasvat
V
Kaul
Phillip D
PD
Squillace
John C
JC
Lieske
Muthuvel
M
Jayachandran
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002417:Cattle; D017886:Durapatite / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D016252:Microscopy, Scanning Tunneling; D008875:Middle Aged; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use / Q000648:ultrastructure; D010974:Platelet Aggregation / Q000187:drug effects*; D053657:Platelet-Rich Plasma / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits
D001672:Biocompatible Materials; D000255:Adenosine Triphosphate; D017886:Durapatite