title: Role of calcifying nanoparticle in the development of hyperplasia and vascular calcification in an animal model.
abstract: OBJECTIVE
  Calcifying nanoparticles (NPs) have been detected recently in calcified human arterial specimens and are involved in the process of calcification. This study was designed to test the hypothesis that human-derived NPs could worsen the response to arterial endothelial injury and induce vascular calcification.
  
  
  METHODS
  The right carotid artery of 24 New Zealand rabbits was injured with an angioplasty balloon. Animals were perfused intravenously with saline (100 mL) during the experiment and divided into three groups: group-A, control; group-B, exposed to NPs (2 mL) obtained from calcified aortic valves; and group-C, exposed to NPs (2 mL) and treated postoperatively with atorvastatin (2.5 mg/kg/24 h). At 30 days, both carotid arteries were removed and examined histologically. Blood measurements were monitored during the study.
  
  
  RESULTS
  The intimal hyperplasia area was significantly larger in the injured right carotid artery compared with the left unoperated carotid artery in all groups. There was no significant variation in medial area between groups. Morphometrically, the intima/media ratio (IMR) was significantly higher in damaged carotids compared with controls. A significant increase of IMR was found in group-B (1.81 ± 0.41) compared with group-A (0.38 ± 0.59; p = .004) or group-C (0.89 ± 0.79; p = .035). Differences between groups C and A were not significant (p = .064). Calcifications were observed in six animals, all of which had been exposed to NPs (4 in group-B, 2 in group-C, p = .027). Plasma levels of cholesterol and triglycerides remained stable.
  
  
  CONCLUSIONS
  This research confirms the ability of systemic inoculation of human-derived NPs to accelerate hyperplasia and stimulate calcification in localized areas of arteries previously submitted to endothelial damage, while it was harmless in healthy arteries. Atorvastatin was demonstrated to slow down this process.
authors.affiliation: Division of Vascular Surgery, Hospital Clínico Universitario, Valladolid, Spain. Electronic address: noecen@yahoo.es.
authors.forename: N
authors.initials: N
authors.lastname: Cenizo Revuelta
authors.affiliation: Division of Vascular Surgery, Hospital Clínico Universitario, Valladolid, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Gonzalez-Fajardo
authors.affiliation: Division of Microbiology, Hospital Clínico Universitario, Valladolid, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Bratos
authors.affiliation: Division of Pathology, Hospital Clínico Universitario, Valladolid, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Alvarez-Gago
authors.affiliation: Division of Laboratory Medicine, Hospital Clínico Universitario, Valladolid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Aguirre
authors.affiliation: Division of Vascular Surgery, Hospital Clínico Universitario, Valladolid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Vaquero
mesh_terms: D000800:Angioplasty, Balloon; D000818:Animals; D000069059:Atorvastatin; D059587:Calcifying Nanoparticles / Q000008:administration & dosage / Q000378:metabolism*; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D020212:Carotid Artery Injuries / Q000097:blood / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D006965:Hyperplasia; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D058426:Neointima; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D061205:Vascular Calcification / Q000097:blood / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
chemical_list: D059587:Calcifying Nanoparticles; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D014280:Triglycerides; D002784:Cholesterol; D000069059:Atorvastatin
keywords: Arterial calcification; Atorvastatin; Calcifying nanoparticles; Hyperplasia