title: The results in rodent models of atherosclerosis are not interchangeable: the influence of diet and strain.
abstract: The determinant factors for the development of atherosclerosis in response to dietary cholesterol were examined in two animal models to assess the comparability of results. We studied 128 male Apo E(-/-) and 128LDLr(-/-) mice randomly assigned to baseline (n=8) and 5 groups (n=24 each) that differed only in their dietary fat and cholesterol supplements. At 10, 16, 24 and 32 weeks of age, 8 animals from each group were sequentially sacrificed and the variables analyzed. The lesion sizes changed at different rates but they were predictable and did not differ in complexity. We observed, however, significant differences between strains, particularly in the constitutive expression of liver genes, their metabolic response to dietary cholesterol, their feeding behaviour, their glucose tolerance and the gain in body weight. Both strains presented characteristics that resemble steatohepatitis but manifestations were more severe in LDLr(-/-) mice. The divergent responses indicate that the choice of the diet and the model should be carefully considered in atherosclerosis studies and extrapolations interpreted with caution.
authors.affiliation: Centre de Recerca Biomèdica, Hospital Universitari de Sant Joan, Carrer Sant Joan s/n, 43201-Reus, Spain. jjoven@grupsagessa.com
authors.forename: Jorge
authors.initials: J
authors.lastname: Joven
authors.forename: Anna
authors.initials: A
authors.lastname: Rull
authors.forename: Natàlia
authors.initials: N
authors.lastname: Ferré
authors.forename: Joan Carles
authors.initials: JC
authors.lastname: Escolà-Gil
authors.forename: Judit
authors.initials: J
authors.lastname: Marsillach
authors.forename: Blai
authors.initials: B
authors.lastname: Coll
authors.forename: Carlos
authors.initials: C
authors.lastname: Alonso-Villaverde
authors.forename: Gerard
authors.initials: G
authors.lastname: Aragones
authors.forename: Joan
authors.initials: J
authors.lastname: Claria
authors.forename: Jordi
authors.initials: J
authors.lastname: Camps
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D001835:Body Weight; D002791:Cholesterol, Dietary / Q000009:adverse effects*; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000473:pathology; D005247:Feeding Behavior; D005951:Glucose Tolerance Test; D007249:Inflammation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011897:Random Allocation; D011973:Receptors, LDL / Q000235:genetics*; D015203:Reproducibility of Results
chemical_list: D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D011973:Receptors, LDL