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 b 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.

No abstract