title: Increased atherosclerotic lesion area in apoE deficient mice overexpressing bovine growth hormone.
abstract: Human growth hormone (GH) excess is linked to increased cardiovascular morbidity and mortality. However, little is known about the effect of GH excess on atherosclerosis. We developed a new mouse model to assess the hypothesis that GH overexpression accelerates atherosclerotic lesion formation. apoE(-/-) mice were crossed with bovine GH (bGH) transgenic mice to yield apoE(-/-) mice overexpressing bGH (apoE(-/-)/bGH). The mice were fed either standard or Western diet. At 22 weeks, atherosclerotic lesion area of thoracic aorta was larger in apoE(-/-)/bGH mice compared with littermate apoE(-/-) mice fed either diet (standard: +161+/-50%, Western: +430+/-134%). Aortic sinus lesions were more severe in apoE(-/-)/bGH mice fed standard diet compared with littermate apoE(-/-) mice. apoE(-/-)/bGH mice had lower (VLDL+LDL)/HDL ratios compared with littermate apoE(-/-) mice, while systolic blood pressure was higher in apoE(-/-)/bGH mice, irrespective of diet. The levels of serum amyloid A and hepatic CRP mRNA were higher in apoE(-/-)/bGH mice than in littermate apoE(-/-) mice. In conclusion, this study shows that excess GH augments the development of atherosclerosis in apoE(-/-) mice. The mechanisms could be direct effects of GH on cellular processes in the vessel wall or the result of concomitant processes such as hypertension or a general inflammatory state.
authors.affiliation: Department of Physiology, Göteborg University, Göteborg, Sweden.
authors.forename: Irene J
authors.initials: IJ
authors.lastname: Andersson
authors.forename: Anna
authors.initials: A
authors.lastname: Ljungberg
authors.forename: Lennart
authors.initials: L
authors.lastname: Svensson
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Gan
authors.forename: Jan
authors.initials: J
authors.lastname: Oscarsson
authors.forename: Göran
authors.initials: G
authors.lastname: Bergström
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology*; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism; D003433:Crosses, Genetic; D017931:DNA Primers; D004032:Diet; D004195:Disease Models, Animal; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D000685:Serum Amyloid A Protein / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D017931:DNA Primers; D000685:Serum Amyloid A Protein; D013006:Growth Hormone; D002097:C-Reactive Protein