title: Complex porcine model of atherosclerosis: induction of early coronary lesions after long-term hyperlipidemia without sustained hyperglycemia.
abstract: BACKGROUND
  The incidence of coronary artery disease (CAD) is still increasing in industrialized countries and it is even higher in diabetic patients. For experimental studies investigating the pathophysiology of CAD, the use of an animal model comparable with the pathological situation in patients is crucial.
  
  
  OBJECTIVE
  To develop a model of advanced coronary atherosclerosis with induction of hyperlipidemia and hyperglycemia in domestic pigs.
  
  
  METHODS
  Six pigs were fed a standard pig chow (controls), two were fed a 2% cholesterol and 17% coconut fat diet (Chol group), and two pigs received a 4% cholesterol and 17% coconut fat diet combined with streptozotocin (STZ) injections to induce diabetes (High Chol+STZ group). Serum lipid and plasma glucose values were analyzed, and histochemical staining for morphometric analysis and immunohistochemistry were performed.
  
  
  RESULTS
  Pigs on the hyperlipidemic diet had elevated mean (+/- SD) serum lipid levels (total cholesterol 5.05+/-1.45 mmol/L [Chol] and 5.03+/-2.41 mmol/L [High Chol+STZ] versus 2.09+/-0.23 mmol/L [controls]). Histopathological evaluation revealed an initial stage of coronary atherosclerosis. None of the STZ-treated pigs showed a sustained elevation of plasma glucose (mean glucose before STZ injection was 5.11+/-0.94 mmol/L and thereafter was 6.03+/-2.39 mmol/L) or a decline in pancreatic beta cells.
  
  
  CONCLUSIONS
  The current data suggest that the domestic porcine model is not suitable to create severe CAD using an atherogenic diet in combination with STZ injections for experimental interventional vascular research. This may be due to different STZ sensitivities among species. However, hyperlipidemia induced early pathological lesions in coronary arteries resembling initial stages of atherosclerosis without severe luminal narrowing.
authors.affiliation: Department of Cardiology, Charité-Campus Benjamin Franklin, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Artinger
authors.forename: Carolin
authors.initials: C
authors.lastname: Deiner
authors.forename: Christoph
authors.initials: C
authors.lastname: Loddenkemper
authors.forename: Peter L
authors.initials: PL
authors.lastname: Schwimmbeck
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schultheiss
authors.forename: Klaus
authors.initials: K
authors.lastname: Pels