title: The cardiovascular phenotype of a mouse model of acromegaly.
abstract: BACKGROUND
  Although, it is accepted that there is an excess of cardiovascular mortality in acromegaly, it is uncertain whether this is due to the direct effects of growth hormone-induced-cardiomyopathy or is a consequence of atherosclerosis secondary to the metabolic syndrome often observed in this condition. Direct comparison of a mouse model of acromegaly to a mouse model of Laron's syndrome allowed us to carry out detailed phenotyping and better understand the role GH plays in the circulatory system.
  
  
  RESULTS
  Transgenic mice that overexpress the growth hormone gene (GH) developed gigantism, including insulin resistance and higher blood pressures commensurate with increased body mass. In these giant mice, the hearts were hypertrophied but haemodynamic studies suggested contractile function was normal. Segments of small arteries mounted in a pressure myograph showed vascular wall hypertrophy but a preserved lumen diameter. Vascular contractile function was normal. Mice in which the GH receptor gene was disrupted or 'knocked out' were dwarf and had low blood pressure, small hearts and blood vessels but a normally functioning circulation. Correlations of body mass with cardiovascular parameters suggested that blood pressure and structural characteristics develop in line with body size.
  
  
  CONCLUSIONS
  In this transgenic mouse model of acromegaly, there is cardiac and vascular hypertrophy commensurate with GH excess but normal function. Our findings support the contention that the excess mortality in this condition may be due to the development of hypertrophic cardiomyopathy rather than increased rates of atherosclerotic coronary artery disease.
authors.affiliation: School of Clinical and Laboratory Sciences, University of Manchester, Manchester, UK.
authors.forename: Ashley S
authors.initials: AS
authors.lastname: Izzard
authors.forename: Michael
authors.initials: M
authors.lastname: Emerson
authors.forename: Sukhpal
authors.initials: S
authors.lastname: Prehar
authors.forename: Ludwig
authors.initials: L
authors.lastname: Neyses
authors.forename: Peter
authors.initials: P
authors.lastname: Trainer
authors.forename: Edward O
authors.initials: EO
authors.lastname: List
authors.forename: John J
authors.initials: JJ
authors.lastname: Kopchick
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Heagerty
mesh_terms: D000172:Acromegaly / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D002319:Cardiovascular System / Q000503:physiopathology; D013006:Growth Hormone / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000502:physiology; D009929:Organ Size; D010641:Phenotype
chemical_list: D013006:Growth Hormone