Parathyroid hormone-related protein (PTHrP) signal cascade modulates myocardial dysfunction in the pressure overloaded heart

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