TY  - JOUR
A1  - Biermann, Daniel
A1  - Heilmann, Andreas
A1  - Didié, Michael
A1  - Schlossarek, Saskia
A1  - Wahab, Azadeh
A1  - Grimm, Michael
A1  - Römer, Maria
A1  - Reichenspurner, Hermann
A1  - Sultan, Karim R.
A1  - Steenpass, Anna
A1  - Ergün, Süleyman
A1  - Donzelli, Sonia
A1  - Carrier, Lucie
A1  - Ehmke, Heimo
A1  - Zimmermann, Wolfram H.
A1  - Hein, Lutz
A1  - Böger, Rainer H.
A1  - Benndorf, Ralf A.
T1  - Impact of AT2 Receptor Deficiency on Postnatal Cardiovascular Development
JF  - PLoS One
N2  - Background: The angiotensin II receptor subtype 2 (AT2 receptor) is ubiquitously and highly expressed in early postnatal life. However, its role in postnatal cardiac development remained unclear. 
Methodology/Principal Findings: Hearts from 1, 7, 14 and 56 days old wild-type (WT) and AT2 receptor-deficient (KO) mice were extracted for histomorphometrical analysis as well as analysis of cardiac signaling and gene expression. Furthermore, heart and body weights of examined animals were recorded and echocardiographic analysis of cardiac function as well as telemetric blood pressure measurements were performed. Moreover, gene expression, sarcomere shortening and calcium transients were examined in ventricular cardiomyocytes isolated from both genotypes. KO mice exhibited an accelerated body weight gain and a reduced heart to body weight ratio as compared to WT mice in the postnatal period. However, in adult KO mice the heart to body weight ratio was significantly increased most likely due to elevated systemic blood pressure. At postnatal day 7 ventricular capillarization index and the density of \(\alpha\)-smooth muscle cell actin-positive blood vessels were higher in KO mice as compared to WT mice but normalized during adolescence. Echocardiographic assessment of cardiac systolic function at postnatal day 7 revealed decreased contractility of KO hearts in response to beta-adrenergic stimulation. Moreover, cardiomyocytes from KO mice showed a decreased sarcomere shortening and an increased peak Ca\(^{2+}\) transient in response to isoprenaline when stimulated concomitantly with angiotensin II. 
Conclusion: The AT2 receptor affects postnatal cardiac growth possibly via reducing body weight gain and systemic blood pressure. Moreover, it moderately attenuates postnatal vascularization of the heart and modulates the beta adrenergic response of the neonatal heart. These AT2 receptor-mediated effects may be implicated in the physiological maturation process of the heart.
KW  - mice
KW  - II type-2 receptor
KW  - human endothelial cells
KW  - chronic kidney disease
KW  - angiotensin II
KW  - blood pressure
KW  - in vitro
KW  - cardiac hyperthrophy
KW  - tube formation
KW  - rat heart
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134902
VL  - 7
IS  - 10
ER  - 
TY  - JOUR
A1  - Montes-Cobos, Elena
A1  - Li, Xiao
A1  - Fischer, Henrike J.
A1  - Sasse, André
A1  - Kügler, Sebastian
A1  - Didié, Michael
A1  - Toischer, Karl
A1  - Fassnacht, Martin
A1  - Dressel, Ralf
A1  - Reichardt, Holger M.
T1  - Inducible Knock-Down of the Mineralocorticoid Receptor in Mice Disturbs Regulation of the Renin-Angiotensin-Aldosterone System and Attenuates Heart Failure Induced by Pressure Overload
JF  - PLoS One
N2  - Mineralocorticoid receptor (MR) inactivation in mice results in early postnatal lethality. Therefore we generated mice in which MR expression can be silenced during adulthood by administration of doxycycline (Dox). Using a lentiviral approach, we obtained two lines of transgenic mice harboring a construct that allows for regulatable MR inactivation by RNAi and concomitant expression of eGFP. MR mRNA levels in heart and kidney of inducible MR knock-down mice were unaltered in the absence of Dox, confirming the tightness of the system. In contrast, two weeks after Dox administration MR expression was significantly diminished in a variety of tissues. In the kidney, this resulted in lower mRNA levels of selected target genes, which was accompanied by strongly increased serum aldosterone and plasma renin levels as well as by elevated sodium excretion. In the healthy heart, gene expression and the amount of collagen were unchanged despite MR levels being significantly reduced. After transverse aortic constriction, however, cardiac hypertrophy and progressive heart failure were attenuated by MR silencing, fibrosis was unaffected and mRNA levels of a subset of genes reduced. Taken together, we believe that this mouse model is a useful tool to investigate the role of the MR in pathophysiological processes.
KW  - cells
KW  - balance
KW  - polarization
KW  - transgenic rats
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137575
VL  - 10
IS  - 11
ER  -