Parathyroid hormone-related peptide improves contractile  function of stunned myocardium in rats and pigs

Jansen, Johanna; Gres, Petra; Umschlag, Christian; Heinzel, Frank R.; Degenhardt, Heike; Schlüter, Klaus‐Dieter; Heusch, Gerd; Schulz, Rainer

doi:10.1152/ajpheart.01037.2001

Cited by 37 publications

(23 citation statements)

References 29 publications

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“…This is in accordance with our recent histological data demonstrating a PTH-mediated decrease in infarct size 30 days after MI associated with a diminished postinfarct remodeling reflected by a reduced wall thinning without detectable signs of hypertrophy (26). Furthermore, PTH treatment was shown to increase myocardial blood flow by a reduction of coronary artery resistance in stunned myocardium of pigs and rats (13). Moreover, PTH treatment after coronary artery ligation in dogs revealed a tissue-protecting effect on the myocardium, ameliorating LV function and preventing the development of cardiogenic shock (12).…”

Section: Discussionsupporting

confidence: 92%

Comparison of parathyroid hormone and G-CSF treatment after myocardial infarction on perfusion and stem cell homing

Hüber

Fischer²,

Brunner³

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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Mobilization of stem cells by granulocyte colony-stimulating factor (G-CSF) was shown to have protective effects after myocardial infarction (MI); however, clinical trials failed to be effective. In search for alternative cytokines, parathyroid hormone (PTH) was recently shown to promote cardiac repair by enhanced neovascularization and cell survival. To compare the impact of the two cytokines G-CSF and PTH on myocardial perfusion, mice were noninvasively and repetitively investigated by pinhole single-photon emission computed tomography (SPECT) after MI. Mobilization and homing of bone marrow-derived stem cells (BMCs) was analyzed by fluorescence-activated cell sorter (FACS) analysis. Mice (C57BL/6J) were infarcted by left anterior descending artery ligation. PTH (80 mug/kg) and G-CSF (100 mug/kg) were injected for 5 days. Perfusion defects were determined by (99m)Tc-sestamibi SPECT at days 6 and 30 after MI. The number of BMCs characterized by Lin(-)/Sca-1(+)/c-kit(+) cells in peripheral blood and heart was analyzed by FACS. Both G-CSF and PTH treatment resulted in an augmented mobilization of BMCs in the peripheral blood. Contrary to G-CSF and controls, PTH and the combination showed significant migration of BMCs in ischemic myocardium associated with a significant reduction of perfusion defects from day 6 to day 30. A combination of both cytokines had no additional effects on migration and perfusion. In our preclinical model, SPECT analyses revealed the functional potential of PTH reducing size of infarction together with an enhanced homing of BMCs to the myocardium in contrast to G-CSF. A combination of both cytokines did not improve the functional outcome, suggesting clinical applications of PTH in ischemic heart diseases.

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Section: Discussionsupporting

confidence: 92%

Comparison of parathyroid hormone and G-CSF treatment after myocardial infarction on perfusion and stem cell homing

Hüber

Fischer²,

Brunner³

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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“…Thus, comparing the obtained results with the data of our previous studies [18], as well as with the latest published findings [24][25][26], we can assume that the increase of PTH levels in blood of patients suffering from heart failure has a compensatory modulating significance for supporting heart activity.…”

Section: Resultssupporting

confidence: 81%

Dose-dependent effect of parathyroid hormone 1-34 fragment and its influence mechanism on the functional activity of isolated heart

Ter-Markosyan¹,

Harutunyan²,

Sargsyan³

et al. 2012

OJMIP

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The present investigation is the continuation of our prior clinical studies on the content of parathyroid hormone (PTH), its paracrine analog, parathyroid hormone-related protein (PTHrP) and electrolytes in blood of patients with heart failure. The results of these studies formed the basis for the nomination of the hypothesis on PTH and PTHrP compensatorymodulating effect on the contractile activity of heart. The objective of this study is to elucidate the mechanism of the compensatory-modulating effect of PTH on heart functional activity, which is realized by the study of effective doses of PTH by pharmacological analysis, using different inhibitors. The dose-dependent effect of PTH on the heart contraction rate and amplitude is studied on the frog isolated heart by the method of non-invasive registration of heart contractile activity. The method is based on the photoelectric principle of the reflected from the contractile object light ray transformation into an electric signaling. It is shown that the most effective dose that has positive chronotropic and inotropic effects on heart is 10 -10 M hormone. To clarify the mechanism of PTH physiological dose action on the contractile activity of heart PTH 1-34 is combined with Ca-channel as well as phosphodiesterase blockers. The mentioned substances are applied based on the fact that PTH effect on target cells is mediated by secondary messengers, particularly calcium ions and cAMP. Based on the data obtained by combination of hormone with Verapamil (10 -5 M) and Theophylline (10 -4 M), we concluded on the involvement of calcium ions in the realization of chronotropic and cAMP in the inotropic effects on the heart.

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“…As endothelial cells are the main source of PTHrP in ventricles this most likely represents up-regulation of endothelial-derived PTHrP. Noteworthy, PTHrP can be considered as a cardioprotective protein reducing the susceptibility of endothelial cells against apoptosis and increasing cardiac function [10,11]. On the other hand nicotine has been shown to induce pulmonary fibroblast trans-differentiation via down-regulation of PTHrP receptors [12].…”

Section: Introductionmentioning

confidence: 99%

Effects of Nicotine on PTHrP and PTHrP Receptor Expression in Rat Coronary Endothelial Cells

Röthig¹,

Schreckenberg²,

Weber³

et al. 2012

Cell Physiol Biochem

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Aims: The study was aimed to investigate whether nicotine affects endothelial expression of PTHrP and PTHrP receptor, a peptide system involved in endothelial protection against apoptosis. Methods: Isolated and cultured rat coronary endothelial cells were used. Immunoblot techniques were used to study activation of mitogen-activated protein (MAP) kinases and to quantify PTHrP and PTHrP receptor expression. Real-time RT-PCR was used to quantify PTHrP, PTHrP-receptor, bcl-2, and bax mRNA expression. The rate of apoptosis was determined by HOE33258 staining and confirmed by quantification of the bcl-2-to-bax ratio. In vitro data were compared to hearts from rats exposed to cigarette smoking. Results: Nicotine induced PTHrP protein expression at nanomolar levels and small increases of PTHrP release (≈8%). Antagonists directed against the α7 subunit of cholinergic receptors, the most prominent isoform, attenuated nicotine-dependent increases of PTHrP expression. This effect of nicotine was p38 MAPK dependent. Nicotine at micromolar concentrations reduced PTHrP receptor expression. In vitro and in vivo we found a correlation between PTHrP receptor expression and bcl-2 expression. Conclusion: Nicotine induces PTHrP expression in endothelial cells but excessive concentrations of nicotine reduce PTHrP receptor expression thereby attenuating any protective effects of PTHrP against apoptosis.

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Parathyroid hormone-related peptide improves contractile function of stunned myocardium in rats and pigs

Cited by 37 publications

References 29 publications

Comparison of parathyroid hormone and G-CSF treatment after myocardial infarction on perfusion and stem cell homing

Comparison of parathyroid hormone and G-CSF treatment after myocardial infarction on perfusion and stem cell homing

Dose-dependent effect of parathyroid hormone 1-34 fragment and its influence mechanism on the functional activity of isolated heart

Effects of Nicotine on PTHrP and PTHrP Receptor Expression in Rat Coronary Endothelial Cells

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