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Impairment of cardiac function and bioenergetics in adult transgenic mice overexpressing the bovine growth hormone gene

Item Type:Article
Title:Impairment of cardiac function and bioenergetics in adult transgenic mice overexpressing the bovine growth hormone gene
Creators Name:Bollano, E. and Omerovic, E. and Bohlooly-Y, M. and Kujacic, V. and Madhu, B. and Tornell, J. and Isaksson, O. and Soussi, B. and Schulze, W. and Fu, M.L.X. and Matejka, G. and Waagstein, F. and Isgaard, J.
Abstract:Cardiovascular abnormalities represent the major cause of death in patients with acromegaly. We evaluated cardiac structure, function, and energy status in adult transgenic mice overexpressing bovine GH (bGH) gene. Female transgenic mice expressing bGH gene (n = 11) 8 months old and aged matched controls (n = 11) were used. They were studied with two-dimensional guided M-mode and Doppler echocardiography. The animals (n = 6) for each group were examined with 31P magnetic resonance spectroscopy to determine the cardiac energy status. Transgenic mice had a significantly higher body weight (BW), 53.2 ± 2.4 vs. 34.6 ± 3.7 g (P < 0.0001) and hypertrophy of left ventricle (LV) compared with normal controls: LV mass/BW 5.6 ± 1.6 vs. 2.7 ± 0.2 mg/g, P < 0.01. Several indexes of systolic function were depressed in transgenic animals compared with controls mice such as shortening fraction 25 ± 3.0% vs. 39.9 ± 3.1%; ejection fraction, 57 ± 9 vs. 77 ± 5; mean velocity of circumferential shortening, 4.5 ± 0.8 vs. 7.0 ± 1.1 circ/sec, p < 0.01. Creatine phosphate-to-ATP ratio was significantly lower in bGH overexpressing mice (1.3 ± 0.08 vs. 2.1 ± 0.23 in controls, P < 0.05). Ultrastructural examination of the hearts from transgenic mice revealed substantial changes of mitochondria. This study provides new insight into possible mechanisms behind the deteriorating effects of long exposure to high level of GH on heart function.
Keywords:Acromegaly, Adenosine Triphosphate, Body Weight, Echocardiography, Energy Metabolism, Gene Expression, Growth Hormone, Heart Diseases, Magnetic Resonance Spectroscopy, Myocardium, Organ Size, Phosphocreatine, Systole, Transgenic Mice, Animals, Cattle, Mice
Publisher:Endocrine Society
Page Range:2229-2235
Date:1 June 2000
Official Publication:http://endo.endojournals.org/cgi/content/abstract/141/6/2229
PubMed:View item in PubMed

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