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Endocrinology Vol. 141, No. 6 2229-2235
Copyright © 2000 by The Endocrine Society

ARTICLES

Impairment of Cardiac Function and Bioenergetics in Adult Transgenic Mice Overexpressing the Bovine Growth Hormone Gene1

Entela Bollano, Elmir Omerovic, Mohammad Bohlooly-Y, Vuk Kujacic, Basetti Madhu, Jan Tornell, Olle Isaksson, Bassam Soussi, Wolfgang Schulze, Michael L. X. Fu, Goran Matejka, Finn Waagstein and Jorgen Isgaard

Wallenberg and Lundberg Laboratories (E.B., E.O., B.M., B.S., M.L.X.F., F.W.), Research Center for Endocrinology and Metabolism (O.I., G.M., J.I.), Department of Internal Medicine, Department of Clinical Physiology (V.K.), Sahlgrenska University Hospital, 413 45 Goteborg, Sweden; Department of Physiology (M.B., J.T.), Goteborg University, Medicinaregatan 7B, 413 90, Goteborg, Sweden; Max-Delbrück-Centrum fur Molekulare Medizin (W.S.), MDC, Robert-Rossle-Strasse 10, Berlin, D-13125, Germany

Address all correspondence and requests for reprints to: Jorgen Isgaard, M.D., Ph.D., Research Center for Endocrinology and Metabolism, Sahlgrenska University Hospital, 413 45 Goteborg, Sweden. E-mail: jorgen.isgaard{at}ss.gu.se

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.




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