TY - JOUR A1 - Frantz, Stefan A1 - Klaiber, Michael A1 - Baba, Hideo A. A1 - Oberwinkler, Heinz A1 - Völker, Katharina A1 - Gaßner, Birgit A1 - Bayer, Barbara A1 - Abeßer, Marco A1 - Schuh, Kai A1 - Feil, Robert A1 - Hofmann, Franz A1 - Kuhn, Michaela T1 - Stress-dependent dilated cardiomyopathy in mice with cardiomyocyte-restricted inactivation of cyclic GMP-dependent protein kinase I JF - European Heart Journal N2 - Aims: Cardiac hypertrophy is a common and often lethal complication of arterial hypertension. Elevation of myocyte cyclic GMP levels by local actions of endogenous atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) or by pharmacological inhibition of phosphodiesterase-5 was shown to counter-regulate pathological hypertrophy. It was suggested that cGMP-dependent protein kinase I (cGKI) mediates this protective effect, although the role in vivo is under debate. Here, we investigated whether cGKI modulates myocyte growth and/or function in the intact organism. Methods and results: To circumvent the systemic phenotype associated with germline ablation of cGKI, we inactivated the murine cGKI gene selectively in cardiomyocytes by Cre/loxP-mediated recombination. Mice with cardiomyocyte-restricted cGKI deletion exhibited unaltered cardiac morphology and function under resting conditions. Also, cardiac hypertrophic and contractile responses to β-adrenoreceptor stimulation by isoprenaline (at 40 mg/kg/day during 1 week) were unaltered. However, angiotensin II (Ang II, at 1000 ng/kg/min for 2 weeks) or transverse aortic constriction (for 3 weeks) provoked dilated cardiomyopathy with marked deterioration of cardiac function. This was accompanied by diminished expression of the \([Ca^{2+}]_i\)-regulating proteins SERCA2a and phospholamban (PLB) and a reduction in PLB phosphorylation at Ser16, the specific target site for cGKI, resulting in altered myocyte \(Ca^{2+}_i\) homeostasis. In isolated adult myocytes, CNP, but not ANP, stimulated PLB phosphorylation, \(Ca^{2+}_i\)-handling, and contractility via cGKI. Conclusion: These results indicate that the loss of cGKI in cardiac myocytes compromises the hypertrophic program to pathological stimulation, rendering the heart more susceptible to dysfunction. In particular, cGKI mediates stimulatory effects of CNP on myocyte \(Ca^{2+}_i\) handling and contractility. KW - cyclic KW - GMPcGMP-dependent protein kinase I KW - cardiac hypertrophy KW - natriuretic peptide KW - Ca2+i handling Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134693 VL - 34 ER - TY - CHAP A1 - Gaßner, Michael ED - Husty, Ludwig ED - Link, Thomas ED - Pechtl, Joachim T1 - Zwei linienbandkeramische Grubenöfen aus Straubing T2 - Neue Materialien des Bayerischen Neolithikums 4 - Tagung im Kloster Windberg vom 12. bis 14. November 2021 N2 - Im Rahmen bauvorgreifender Untersuchungen durch die Stadtarchäologie Straubing unter Leitung von Frau Ildiko Bősze konnten in den Jahren 2018 und 2019 im Südosten von Straubing, im Bereich des dortigen Wasserwerks, Teile einer älterlinienbandkeramischen Siedlung erfasst werden. Neben einigen Gruben und vier Hausgrundrissen kamen im nördlichen Bereich der Fläche die Überreste zweier Grubenöfen zu Tage, die hier ausführlich besprochen werden sollen. Als in den letzten Jahren selten anzutreffende Befundgattung und aufgrund ihrer auffällig unterschiedlichen Konstruktionsweisen mit und ohne Steinpflasterung bilden die beiden Straubinger Grubenöfen zwei interessante Untersuchungsobjekte. Mit der Verbreitung der Grubenöfen vom Rheinland bis zum Donauknie und der zeitlichen Beschränkung praktisch ausschließlich auf die LBK handelt es sich um ein Konstruktionsprinzip, das in der Zeit vor den ersten Ackerbauern und auch im anschließenden Mittelneolithikum nicht genutzt wurde (Pechtl 2008, 72–74). Es erscheint daher erstrebenswert, die Befunde sowie die anzusprechende Keramik aus den beiden Grubenöfen aufzuarbeiten und vorzulegen. N2 - In the course of preventive investigations by the Communal Archaeology of Straubing lead by Ms. Ildiko Bősze in 2018 and 2019, parts of a settlement dating to the older Linear Pottery (LBK) were recorded in the area of the local waterworks in the southeast of Straubing. In addition to several pits and four houses, the remains of two pit kilns came to light in the northern area of the site. These will be discussed in detail here. Due to their rarity and their strikingly different construction – with and without stone paving – the two pit kilns prove interesting objects of study. With the spread of the pit kilns from the Rhineland to the Danube Bend and chronologically practically exclusively limited to the LBK, their construction provides a design principle not used before the time of the first farmers or in the subsequent Middle Neolithic (Pechtl 2008, 72–74). It therefore seems desirable to process and present the findings and the available pottery from the two pit kilns. KW - Niederbayern KW - Linienbandkeramik KW - Grubenöfen KW - Lower Bavaria KW - Linear Pottery KW - pit kilns Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-328874 PB - Würzburg University Press CY - Würzburg ER -