Cardiac effects of osteostatin in mice.

Abstract

Mouse parathyroid hormone-related peptide (PTHrP) is a peptide hormone consisting of 139 amino acids. It is target of proteolysis resulting in circulation of N- and C-terminal peptides. C-terminal PTHrP peptides act in a PTH/PTHrP receptor-independent way with a minimal peptide sequence required to exert these effects covering amino acids 107-111 also known as osteostatin. Although effects of osteostatin on cardiac hypertrophy have been described in vitro, the in vivo relevance of these findings remained to be defined. The study was performed in two experimental series. In the first series, mice were randomly distributed into placebo or treatment group (each n=7) and osteostatin was administered via osmotic minipumps. In the second series, mice underwent a banding of the thoracic aorta to induce pressure overload and were again randomly distributed into placebo or treatment group (n=9 each). After 14 days, mice were anaesthetized and cardiac function, ECG, and cardiac hypertrophy were determined. Osteostatin increased the expression of ANF and reduced P-wave duration with little effects on cardiac performance in mice without pressure overload. In TAC banded mice, however, osteostatin significantly reduced TAC-induced loss of body weight, induced right ventricular hypertrophy, and reduced P-wave duration again. In osteostatin treated mice with pressure overload, the protein kinase C-dependent phosphorylation of connexin 43 was preserved. In summary, osteostatin attenuated pressure-overload-dependent loss of body weight without affecting left ventricular hypertrophy or left ventricular function but preserved atrial conduction. Osteostatin exerts moderate cardioprotective effects in mice under hemodynamic stress.

• Authors: R Meyer, R Schreckenberg, D Kraus, F Kretschmer, R Schulz, K-D Schlüter
• Journal: Journal of physiology and pharmacology : an official journal of the Polish Physiological Society (J Physiol Pharmacol) Vol. 63 Issue 1 Pg. 17-22 (Feb 2012) ISSN: 1899-1505 [Electronic] Poland
• PMID: 22460456 (Publication Type: Journal Article)

Chemical References

• Connexin 43
• GJA1 protein, mouse
• Parathyroid Hormone-Related Protein
• Peptide Fragments
• RNA, Messenger
• parathyroid hormone-related protein (107-111)
• Atrial Natriuretic Factor

Topics

• Animals
• Aorta, Thoracic (metabolism, physiopathology)
• Atrial Natriuretic Factor (metabolism)
• Body Weight (drug effects)
• Cardiomegaly (chemically induced, metabolism, physiopathology)
• Connexin 43 (biosynthesis, genetics, metabolism)
• Heart (drug effects, physiopathology)
• Male
• Mice
• Mice, Inbred C57BL
• Parathyroid Hormone-Related Protein (pharmacology)
• Peptide Fragments (pharmacology)
• Phosphorylation (drug effects)
• RNA, Messenger (biosynthesis, genetics)
• Ventricular Function, Left (physiology)