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Publication : The cardiovascular phenotype of a mouse model of acromegaly.

First Author  Izzard AS Year  2009
Journal  Growth Horm IGF Res Volume  19
Issue  5 Pages  413-9
PubMed ID  19269870 Mgi Jnum  J:157146
Mgi Id  MGI:4430061 Doi  10.1016/j.ghir.2008.12.006
Citation  Izzard AS, et al. (2009) The cardiovascular phenotype of a mouse model of acromegaly. Growth Horm IGF Res 19(5):413-9
abstractText  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. METHODS AND 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. CONCLUSION: 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.
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