Journal article

Publication year: 2007

Pages: 1156-1162

Journal: European Journal of Heart Failure

Volume number: 9

Issue number: 12

ISSN: 1388-9842

eISSN: 1879-0844

DOI Link: https://doi.org/10.1016/j.ejheart.2007.10.007

Publisher: Wiley

Abstract: 

Background: Pressure overload induces the cardiac expression of parathyroid hormone-related protein (PTHrP). Plasma levels are elevated in patients with heart disease. It is unknown whether this represents an epiphenomenon or suggests involvement in hypertrophy. Aim: To identify a potential role of PTHrP in pressure induced hypertrophy and heart failure.

Methods and results: Pressure load was produced via thoracic aortic constriction (TAC) and application of a PTHrP antagonist (PTHrP(7-34)) via osmotic minipumps in mice. Main findings were confirmed in vitro by exposing isolated adult ventricular mice cardiomyocytes to PTHrP(1-34) (100 nmol/l). TAC treated animals developed myocardial hypertrophy within 2 weeks. The heart weight to body weight ratio increased from 5.02 +/- 0.14 mg/g (sham/vehicle) and 5.16 +/- 0.19 mg/g (sham/antagonist) to 6.59 +/- 0.85 mg/g (TAC/vehicle) and 7.07 +/- 0.80 mg/g (TAC/antagonist) (each n=6-8;p < 0.05 for TAC vs. sham; not significantly different between TAC groups). In parallel, the expression of atrial natriuretic factor increased. Cardiac dysfunction (+dP/dt, -dP/dt), however, was significantly lower in TAC mice receiving the antagonist, and SERCA2 expression was higher. Isolated cardiomyocytes exposed to PTHrP(1-34) developed reduced cell shortening. This reduction in cell function was abolished in the co-presence of the antagonist.

Conclusion: PTHrP contributes to the progression of cardiac dysfunction in the pressure overloaded heart. (c) 2007 European Society of Cardiology. Published by Elsevier B.V All rights reserved.

Harvard Citation style: Meyer, R., Schreckenberg, R., Kretschmer, F., Bittig, A., Conzelmann, C., Grohe, C., et al. (2007) Parathyroid hormone-related protein (PTHrP) signal cascade modulates myocardial dysfunction in the pressure overloaded heart, European Journal of Heart Failure, 9(12), pp. 1156-1162. https://doi.org/10.1016/j.ejheart.2007.10.007

APA Citation style: Meyer, R., Schreckenberg, R., Kretschmer, F., Bittig, A., Conzelmann, C., Grohe, C., & Schlueter, K. (2007). Parathyroid hormone-related protein (PTHrP) signal cascade modulates myocardial dysfunction in the pressure overloaded heart. European Journal of Heart Failure. 9(12), 1156-1162. https://doi.org/10.1016/j.ejheart.2007.10.007