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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, RESULTS. Meshes: Animals, Cells, Cultured, Disease Models, Animal, Disease Progression, Gene Expression, Hypertrophy, Left Ventricular, Immunoblotting, Male, Mice, Mice, Inbred C57BL, Myocytes, Cardiac, Parathyroid Hormone-Related Protein, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Ventricular Dysfunction, Left, Ventricular Pressure.
user
Does parathyroid hormone-related protein ( PTHrP ) signal cascade modulate myocardial dysfunction in the pressure overloaded heart? Context: 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. To identify a potential role of PTHrP in pressure induced hypertrophy and heart failure. 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.
assistant
PTHrP contributes to the progression of cardiac dysfunction in the pressure overloaded heart. Final Decision: yes