title: Diet induced mild hypercholesterolemia in pigs: local and systemic inflammation, effects on vascular injury - rescue by high-dose statin treatment.
abstract: OBJECTIVE
  The aim of the present study was to comprehensively evaluate systemic and local inflammation as well as progression of vascular inflammation in normal and mechanically injured vessels in a large animal model of mild hypercholesterolemia. Our aim was also to test the effect of high-dose statin treatment on these processes.
  
  
  METHODS
  Pigs were kept for 120 days on a standard diet (SD, n=7), high-cholesterol diet (HCD, n=7) or high-cholesterol diet with Atorvastatin starting after 50 days (STATIN, n=7). Left carotid artery balloon injury was conducted in all groups after 60 days of diet treatment. Biochemical analysis together with evaluation of blood and tissue markers of vascular injury and inflammation were performed in all groups at the end of experiment.
  
  
  RESULTS
  HCD compared to SD induced systemic inflammation demonstrated by increased number of circulating monocytes and lymphocytes. HCD compared to SD induced also local inflammation demonstrated by adipocyte hypertrophy and infiltration of T-lymphocytes in abdominal white adipose tissue, activation of hepatic stellate cells with infiltration of T- and B-lymphocytes and macrophages in the liver and increased macrophage content in lung parenchyma. These changes were accompanied by increased Intima/Media thickness, stenosis, matrix deposition and activated T-cell infiltrates in injured but not in uninjured contralateral carotid artery as we previously reported. The treatment with high-dose statin attenuated all aspects of systemic and local inflammation as well as pathological changes in injured carotid artery.
  
  
  CONCLUSIONS
  Diet related mild hypercholesterolemia induce systemic and local inflammation in the liver, lung and adipose tissue that coincide with enhanced inflammation of injured vessel but is without deleterious effect on uninjured vessels. High dose statin attenuated systemic and local inflammation and protected injured vessels. However, finding exact role of reduced systemic and remote inflammation in vascular protection requires further studies.
authors.affiliation: Department of Surgery and Interdisciplinary Medicine, University of Milano-Bicocca, Milano, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Busnelli
authors.forename: Stefano
authors.initials: S
authors.lastname: Manzini
authors.forename: Alberto
authors.initials: A
authors.lastname: Froio
authors.forename: Alessia
authors.initials: A
authors.lastname: Vargiolu
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Cerrito
authors.forename: Ryszard T
authors.initials: RT
authors.lastname: Smolenski
authors.forename: Massimo
authors.initials: M
authors.lastname: Giunti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cinti
authors.forename: Augusta
authors.initials: A
authors.lastname: Zannoni
authors.forename: Biagio Eugenio
authors.initials: BE
authors.lastname: Leone
authors.forename: Monica
authors.initials: M
authors.lastname: Forni
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Bacci
authors.forename: Giorgio Maria
authors.initials: GM
authors.lastname: Biasi
authors.forename: Roberto
authors.initials: R
authors.lastname: Giovannoni
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Lavitrano
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000473:pathology; D000818:Animals; D001706:Biopsy; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004032:Diet / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D006984:Hypertrophy; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D007958:Leukocyte Count; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008214:Lymphocytes; D008264:Macrophages; D009000:Monocytes; D050507:Subcutaneous Fat, Abdominal / Q000473:pathology; D013552:Swine; D057772:Vascular System Injuries / Q000188:drug therapy / Q000209:etiology / Q000473:pathology
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol