A5063948628- Cardiac Fibrosis and Remodeling
- Cardiac Ischemia and Reperfusion
- Mitochondrial Function and Pathology
- Nitric Oxide and Endothelin Effects
- Signaling Pathways in Disease
- Cardiac electrophysiology and arrhythmias
- Cardiovascular Function and Risk Factors
- ATP Synthase and ATPases Research
- Congenital heart defects research
- Renin-Angiotensin System Studies
- TGF-β signaling in diseases
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Pulmonary Hypertension Research and Treatments
- Connexins and lens biology
- Peptidase Inhibition and Analysis
- Cardiomyopathy and Myosin Studies
- Autophagy in Disease and Therapy
- Cancer-related gene regulation
- Metabolism, Diabetes, and Cancer
- Neuroscience of respiration and sleep
- Heat shock proteins research
- Macrophage Migration Inhibitory Factor
- Calcium signaling and nucleotide metabolism
- Cell death mechanisms and regulation
Justus-Liebig-Universität Gießen
2015-2024
Deutsches Archäologisches Institut, Zentrale
2016
Czech Academy of Sciences, Institute of Physiology
2016
Heinrich Heine University Düsseldorf
2003-2011
Freie Universität Berlin
2011
Charité - Universitätsmedizin Berlin
2011
Deutsches Diabetes-Zentrum e.V.
2002
Background: Anthracyclines, such as doxorubicin (DOX), are potent anticancer agents for the treatment of solid tumors and hematologic malignancies. However, their clinical use is hampered by cardiotoxicity. This study sought to investigate role phosphoinositide 3-kinase γ (PI3Kγ) in DOX-induced cardiotoxicity potential cardioprotective effects PI3Kγ inhibition. Methods: Mice expressing a kinase-inactive or receiving PI3Kγ-selective inhibitors were subjected chronic DOX treatment. Cardiac...
Nitric oxide (NO), a potent regulator of myocardial contractility, has been implicated in the development heart failure; however, no study exists describing relation between expression inducible nitric synthase (iNOS), formation NO vivo, and cardiac contractility. We have therefore generated transgenic (TG) mice overexpressing iNOS under cardiospecific α-myosin heavy chain (α-MHC) promoter. In vitro, activity hearts two lines was 260- to 400-fold above controls (wild type [WT]), but TG were...
Abstract Growth differentiation factor 15 (GDF15) is induced during heart failure development, and may influence different processes in cardiac remodeling. While its anti‐apoptotic action under conditions of ischemia–reperfusion have been shown, it remained unclear if this a broadly protective effect applicable to other apoptotic stimuli. Furthermore, effects on hypertrophy obscure. Therefore, we investigated the GDF15 induction apoptosis ventricular cardiomyocytes. (3 ng/ml) enhanced...
Platelet-derived growth factor BB (PDGF-BB) has been assigned a critical role in vascular and recruitment of perivascular mural cells. The purpose the present study is to investigate signalling events underlying stimulation vasculogenesis mouse embryonic stem (ES) cells by PDGF-BB.PDGF-BB increased sprouting branching capillary-like structures embryoid bodies as evaluated computer-assisted analysis CD31-positive cell structures. It also activated extracellular-regulated kinase 1,2 (ERK1,2)...
Myocardial connexin 43 (Cx43) forms gap junctions and hemichannels, is also present within subsarcolemmal mitochondria. The protein phosphorylated by several kinases including mitogen-activated kinase (MAPK), C (PKC), casein 1 (CK1). A reduction in Cx43 content abrogates myocardial infarct size ischemic preconditioning (IPC). study characterizes the contribution of phosphorylation towards mitochondrial function, hemichannel activity, cardioprotection IPC wild-type (WT) mice which...
The role of inducible nitric-oxide synthase (iNOS) in the pathogenesis heart failure is still a matter controversy. In contrast to early reports favoring contribution iNOS because negative inotropic and apoptotic potential NO, more recent clinical experimental data question causative role. Here we report that transgenic mice with cardiac specific iNOS-overexpression concomitant myoglobin-deficiency (tg-iNOS+/myo–/–) develop signs hypertrophy, ventricular dilatation, interstitial fibrosis....
AimsExpression and activity of the transcription factor AP-1 are enhanced during cardiac remodelling heart failure progression. In order to test if inhibition may limit processes contributing remodelling, ventricular cardiomyocytes mice with overexpression inhibitor JDP2 were analysed under stimulation hypertrophy, apoptosis, or contractile function.
Monoamine oxidase B (MAO-B), a protein localized at the outer mitochondrial membrane, catalyzes oxidative deamination of biogenic amines thereby producing reactive oxygen species (ROS). Increased ROS formation contributes to myocardial ischemia/reperfusion (I/R); however, importance different enzymes for increased I/R-induced and subsequent I/R injury is still matter debate. Here we describe first cardiomyocytes-specific MAO-B knockout mouse test hypothesis that lack cardiomyocyte protects...
Cardiomyocyte maturation during pre- and postnatal development requires multiple intertwined processes, including a switch in energy generation from glucose utilization the embryonic heart towards fatty acid oxidation after birth. This is accompanied by boost mitochondrial mass to increase capacities for oxidative phosphorylation ATP required efficient contraction. Whether cardiomyocyte differentiation paralleled augmented deal with reactive oxygen species (ROS), physiological byproducts of...
Increased mitochondrial reactive oxygen species (ROS) formation is important for the development of right ventricular (RV) hypertrophy (RVH) and failure (RVF) during pulmonary hypertension (PH). ROS molecules are produced in different compartments within cell, with mitochondria known to produce strongest signal. Among ROS-forming proteins, outer-mitochondrial-membrane-located monoamine oxidases (MAOs, type A or B) capable degrading neurotransmitters, thereby producing large amounts ROS. In...
Elevated cardiac levels of nitric oxide (NO) generated by inducible synthase (iNOS) have been implicated in the development heart failure. The surprisingly benign phenotype recently mice with cardiac-specific iNOS overexpression (TGiNOS) provided rationale to investigate whether NO scavenging oxymyoglobin (MbO2) yielding nitrate and metmyoglobin (metMb) is involved preservation myocardial function TGiNOS mice. 1H nuclear magnetic resonance (NMR) spectroscopy was used monitor changes...
The transcription factor AP-1 is a mediator of hypertrophic growth and apoptosis in cardiomyocytes. This puts the center two important processes found failing heart implies that variations (i) composition itself or (ii) additional, interacting factors are responsible for diverse actions AP-1. To test this hypothesis, we performed studies on isolated ventricular cardiomyocytes rat under hypertrophy- apoptosis-inducing conditions.The NO donor SNAP (100 microM), which pro-apoptotic stimulus...
Abstract Transforming growth factor β (TGFβ) expression is induced in the myocardium during transition from compensated hypertrophy to heart failure. In cardiomyocytes, stimulation with TGFβ results restricted contractile function and enhanced apoptosis. Nitric oxide (NO) also induces apoptosis influences cardiac function. Therefore, we wanted know whether NO causally involved TGFβ‐induced isolated ventricular cardiomyocytes of adult rat incubation 1 increased release which was inhibited by...
Insulin-like growth factor (IGF-I) signaling has been implicated to play an important role in regulation of cardiac growth, hypertrophy, and contractile function linked the development age-related congestive heart failure. Here, we address question what extent cardiomyocyte-specific IGF-I is essential for maintenance structural functional integrity adult murine heart. To investigate effects without confounding due overexpression or adaptation during embryonic early postnatal development,...
Abstract Connexin 43 (Cx43), which is highly expressed in the heart and especially cardiomyocytes, interferes with expression of nitric oxide synthase ( NOS ) isoforms. Conversely, Cx43 gene down‐regulated by derived from inducible . Thus, a complex interplay between appears to exist. As cardiac mitochondria are supposed contain , we now investigated isoforms production rate isolated wild‐type Cx43‐deficient (Cx43 Cre‐ER(T)/fl mice hearts. Mitochondria were hearts using differential...
Cardiac remodeling plays a crucial role in the development of heart failure after mycocardial infarction. Besides cardiomyocytes, endothelial cells are recognized to contribute cardiac remodeling. We now investigated processes mesenchymal transition (EndoMT) microvascular rat (MVEC) under hypoxia and paracrine effects on ventricular cardiomyocytes adult rat. Exposure MVECs hypoxia/reoxygenation enhanced TGFβ/SMAD signaling, since phosphorylation, thus activation, SMAD1/5 SMAD2 increased....
The cardiomyocyte-specific knockout (KO) of monoamine oxidase (MAO)-B, an enzyme involved in the formation reactive oxygen species (ROS), reduced myocardial ischemia/reperfusion (I/R) injury vitro. Because sex hormones have a strong impact on MAO metabolic pathways, we analyzed infarct size (IS) following I/R female and male MAO-B KO mice vivo.To induce deletion MAO-B, (Myh6 Cre+/MAO-Bfl/fl) wild-type (WT, Cre-negative MAO-Bfl/fl littermates) were fed with tamoxifen for 2 weeks followed by...
Renin and peroxisome proliferator-activated receptor (PPAR-γ) interact directly with cardiomyocytes influence protein synthesis. We investigated their effects interaction on the size of cardiomyocytes. Effects renin PPAR-γ activation were studied in cultured adult rat ventricular cardiomyocytes, transgenic mice a cardiomyocyte-restricted knockout PPAR-γ, rats overexpressing renin, TGR(mRen2)27. The length width analysed 24 h after administration factors. caused an unexpected effect that was...
Matrix metalloproteinases (MMPs) are identified as modulators of the extracellular matrix in heart failure progression. However, evidence for intracellular effects MMPs is emerging. Pro- and anti-hypertrophic cardiac described. This may be due to various sources different tissue. Therefore, aim present study was determine role hypertrophic growth isolated rat ventricular myocytes.Cardiomyocytes were form tissues hearts by collagenase perfusion. RT-qPCR, western blots, zymography used...