Effect of pathophysiological stressors on the tissue expression of parathyroid hormone-related protein (PTHrP)
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Myocardial infarction and sepsis are considered as devastating diseases in the world. Myocardial ischemia occurs when blockage of one or more coronary arteries reduces the blood flow to the heart. Thus, the amount of oxygen that myocardium receives decreases. Sepsis is a systemic immune response to the infection caused mostly by bacteria.Therefore, the current study aimed to discover the role of high fat diet and ageing in PTHrP system under ischemia/reperfusion in order to explain the so-called obesity paradox, and the role of hypothermia in vital organs, in particular the cardiac expression of PTHrP under endotoxemia. Results suggest an age-dependent expression of PTHrP, being highly elevated in older mice rather than in adult mice. High fat diet affected the expression of PTHrP, its corresponding receptor and the downstream molecules ADRP and PPARgamma. Ischemia/reperfusion increased the mRNA expression of PTHrP and ADRP in the lung but it had no significant effect on PTH-1R and PPARgamma. Results corroborate the activation of the pulmonary paracrine pathway under stress conditions, especially under HFD. Concerning LPS, it induces the PTHrP system in the lung and liver but temperature alteration did not have any significant impact. Left ventricle revealed opposite results compared to other vital organs as LPS downregulated the mRNA of PTHrP and PTH-1R. To verify the downregulation of the PTHrP system in the heart, in vitro experiments performed in the Langendorff apparatus, and in vivo experiments in pigs showed that hypothermia improved mRNA expression of PTHrP in the heart. Hypothermia improved the PTHrP responsiveness in septic hearts as one of the functional parameters of the heart, the LVDP that represents the cardiac contractility, cell shortening of isolated rat heart cells and phosphorylation of ERK (ERK2) were increased under septic conditions.Therefore, we hypothesize that high fat diet may increase the expression of PTHrP system in the lung under ischemia/reperfusion and thereby may improve the epithelial-mesenchymal paracrine cross talk in the lung, the paracrine loop important for pulmonary function. Increase of leptin and other PTHrP downstream targets may stabilize the pulmonary remodeling after ischemia/reperfusion, which describes the obesity paradox. The current data indicate that hypothermia influences the cardiac expression of PTHrP under septic conditions, which suggests that PTHrP participates in improving the cardiac function in this situation.Verknüpfung zu Publikationen oder weiteren Datensätzen
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Giessen : VVB Laufersweiler Verlag