Bitte benutzen Sie diese Kennung, um auf die Ressource zu verweisen: http://dx.doi.org/10.25673/78148
Titel: Influence of serotonin 5-HT4 receptors on responses to cardiac stressors in transgenic mouse models
Autor(en): Gergs, Ulrich
Gerigk, Timo
Wittschier, Jonas
Schmidbaur, Constanze T.
Röttger, Clara
Mahnkopf, Mareen
Edler, Hanna
Wache, Hartmut
Neumann, Joachim
Erscheinungsdatum: 2021
Art: Artikel
Sprache: Englisch
Zusammenfassung: The current study aimed to deepen our knowledge on the role of cardiac 5-HT4 receptors under pathophysiological conditions. To this end, we used transgenic (TG) mice that overexpressed human 5-HT4a receptors solely in cardiac myocytes (5-HT4-TG mice) and their wild-type (WT) littermates that do not have functional cardiac 5-HT4 receptors as controls. We found that an inflammation induced by lipopolysaccharide (LPS) was detrimental to cardiac function in both 5-HT4-TG and WT mice. In a hypoxia model, isolated left atrial preparations from the 5-HT4-TG mice went into contracture faster during hypoxia and recovered slower following hypoxia than the WT mice. Similarly, using isolated perfused hearts, 5-HT4-TG mice hearts were more susceptible to ischemia compared to WT hearts. To study the influence of 5-HT4 receptors on cardiac hypertrophy, 5-HT4-TG mice were crossbred with TG mice overexpressing the catalytic subunit of PP2A in cardiac myocytes (PP2A-TG mice, a model for genetically induced hypertrophy). The cardiac contractility, determined by echocardiography, of the resulting double transgenic mice was attenuated like in the mono-transgenic PP2A-TG and, therefore, largely determined by the overexpression of PP2A. In summary, depending on the kind of stress put upon the animal or isolated tissue, 5-HT4 receptor overexpression could be either neutral (genetically induced hypertrophy, sepsis) or possibly detrimental (hypoxia, ischemia) for mechanical function. We suggest that depending on the underlying pathology, the activation or blockade of 5-HT4 receptors might offer novel drug therapy options in patients.
URI: https://opendata.uni-halle.de//handle/1981185920/80102
http://dx.doi.org/10.25673/78148
Open-Access: Open-Access-Publikation
Nutzungslizenz: (CC BY 4.0) Creative Commons Namensnennung 4.0 International(CC BY 4.0) Creative Commons Namensnennung 4.0 International
Sponsor/Geldgeber: Publikationsfonds MLU
Journal Titel: Biomedicines
Verlag: MDPI
Verlagsort: Basel
Band: 9
Heft: 5
Originalveröffentlichung: 10.3390/biomedicines9050569
Enthalten in den Sammlungen:Open Access Publikationen der MLU

Dateien zu dieser Ressource:
Datei Beschreibung GrößeFormat 
biomedicines-09-00569-v2.pdf3.72 MBAdobe PDFMiniaturbild
Öffnen/Anzeigen