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Myocardial concentration of cardiac troponin T as an early discriminator of mechanisms of cardiac hypertrophy

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Abstract

Measurement of myocardial concentration of the myofibrillar protein, cardiac troponin T (cTnT), was used as a biochemical correlate of myocardial myofibrillar volume fraction to confirm and extend results of histomorphometric studies of changes in myofibrillar density during hypertrophy. Rat models were used to study concentric cardiac hypertrophy due to pressure overload (spontaneous hypertension), eccentric cardiac hypertrophy due to volume overload (administration of minoxidil for 4 weeks), and mixed cardiac hypertrophy due to growth factor stimulation (administration of triiodothyronine for 4 weeks). Mean myocardial cTnT concentration was 583±60 μg/g wet weight tissue in 40 control rats aged 10–20 weeks. We confirmed that pressure overload increased myofibrillar density by up to 30%, whereas volume overload decreased myofibrillar density, in our study, by up to 15%. Growth factor-induced hypertrophy was confirmed to occur by a mixture of processes; while myofibrillar density had increased by 31% at 1 week, it had normalised by 4 weeks. Minoxidil-induced hypertrophy was also confirmed to occur by a mixture of the processes, with myofibrillar density first decreased by 15% at 1 week before normalising by 4 weeks. Progressive, pathological hypertrophy, as modelled with spontaneous hypertension, was confirmed to be associated with abnormal myocardial myofibrillar density. We conclude that myocardial cTnT concentration may be used as a simple and precise biomarker of myofibrillar volume density, which, assessed over time, discriminates early physiological mechanisms involving myocyte thickening from those involving myocyte elongation and may discriminate between physiological and pathological hypertrophy.

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Authors and Affiliations

  1. Safety Assessment, SmithKline Beecham Pharmaceuticals, Welwyn, Hertfordshire, UK

    M. R. Slaughter, S. Campbell & P. J. O’Brien

  2. Safety Sciences Europe (IPC 699), Pfizer Ltd, Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK

    M. R. Slaughter & P. J. O’Brien

Authors
  1. M. R. Slaughter
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  2. S. Campbell
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  3. P. J. O’Brien
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Correspondence to M. R. Slaughter.

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Slaughter, M.R., Campbell, S. & O’Brien, P.J. Myocardial concentration of cardiac troponin T as an early discriminator of mechanisms of cardiac hypertrophy. Comp Clin Path 13, 59–64 (2004). https://doi.org/10.1007/s00580-004-0522-6

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  • DOI: https://doi.org/10.1007/s00580-004-0522-6

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