A Cardiac Mouse Model for Nongenomic Mineralocorticoid Receptor Effects
Journal Title: Journal of Advances in Medicine and Medical Research - Year 2017, Vol 22, Issue 7
Abstract
Aim: As a ligand-dependent transcription factor the mineralocorticoid receptor (MR) regulates water and electrolyte homeostasis in epithelial tissues but also plays a crucial role in the pathogenesis of cardiovascular diseases. In addition to its genomic effects, via the glucocorticoid response elements, rapid interactions with cytosolic signaling cascades have been described, but the physiological or pathophysiological role of this nongenomic MR pathway is still hardly known. Study Design: Transgenic and wild type mice (FVB/N background) of random sex were used in this study. Experimental groups (n = 8-10 for each subgroup) were: A) Cardiac function and gene expression at six months of age; B) Cardiac function and gene expression at twelve months of age; C) Cardiac function at six months of age after 4 weeks aldosterone/NaCl treatment. Place and Duration of Study: Institute for Pharmacology and Toxicology, Medical Faculty of the Martin Luther University Halle-Wittenberg, between June 2008 and November 2011. Methodology: To investigate the cardiac nongenomic MR effects in vivo, we generated a transgenic (TG) mouse model with cardiomyocyte-specific overexpression of a truncated variation of the human MR (hMRDEF). Characterization of six and twelve months old mice focused on cardiac function, electrical activity, and gene transcription under baseline and stimulation conditions by either isoproterenol or aldosterone/NaCl treatment. Results: Whereas overexpression of a full-length MR in the heart was lethal, the phenotype of the hMRDEF-TG mouse seemed inconspicuously. Noteworthy, the nongenomic MR effect modulated the cardiac transcription of the α-subunit of the voltage-gated potassium channel ERG, which resulted in prolonged intraventricular electrical activity. Therefore, nongenomic MR signaling pathways may be responsible for MR-associated cardiac arrhythmias. Conclusion: Our findings demonstrate that nongenomic MR effects can modulate cardiac electrophysiology in vivo and therefore indicate an involvement of nongenomic MR signaling pathways in the pathogenesis of cardiac dysfunction.
Authors and Affiliations
Sabrina Winter, Barbara Schreier, Ulrich Gergs, Claudia Grossmann, Sindy Rabe, Igor B. Buchwalow, Michael Gekle, Joachim Neumann
Keywords
Related Articles
- EP ID EP312365
- DOI 10.9734/JAMMR/2017/34389
- Views 112
- Downloads 0
Anemia and Dietary Habits among Pregnant Women in Jazan, Saudi Arabia
Aims: To determine the prevalence of anaemia among pregnant women in Jazan in the Southern region of Saudi Arabia, and identify some food habits of pregnant women. The association between having anaemia and some maternal...
The Efficacy of QuikClot Combat Gauze, Fluid Resuscitation and Movement on Hemorrhage Control in a Porcine Model of Hypothermia
Aims: The purpose of this study was to compare the effectiveness QuikClot Combat Gauze (QCG) to a control group on hemorrhage control and investigate the effects of intravenous volume resuscitation on rebleeding and move...
Common Infectious Etiologies of Acute Febrile Illness in a Remote Geographical Location: Could Scrub Typhus be the Most Common Cause?
Background: Disease burden of acute febrile illness due to infectious etiologies is under reported in various parts of India including Sikkim due to lack of laboratory confirmation. Undifferentiated febrile illnesses com...
Endoscopic Treatment of Middle Ear Myoclonus with Stapedius and Tensor Tympani Section: A New Minimally-Invasive Approach
Aims: We describe a new, entirely endoscopic surgical technique for treatment of middle ear myoclonus. Case Presentation: In our patient, the stapedius and tensor tympani tendons were sectioned to control chronic middle...
Effect of Ramipril Treatment on Proteinuria and Advanced Glycation End Products in Type 2 Diabetes Mellitus Patients with Nephropathy: One Year Follow up Study
Aims: The present study was carried out to evaluate the effect of angiotensin converting enzyme inhibitor (ACEI) therapy on proteinuria and serum advanced glycation end products (AGEs) level in type 2 diabetes mellitus (...