7 results on '"Görlach, Agnes"'
Search Results
2. Circular RNA maps paving the road to biomarker development?
- Author
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Görlach, Agnes and Holdenrieder, Stefan
- Subjects
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CIRCULAR RNA , *BIOMARKERS , *NUCLEOTIDE sequencing , *SPLICEOSOMES , *EPIGENETICS - Published
- 2017
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3. Prolyl-hydroxylase inhibition induces SDF-1 associated with increased CXCR4+/CD11b+ subpopulations and cardiac repair.
- Author
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Ghadge, Santhosh, Messner, Moritz, Van Pham, Thi, Doppelhammer, Maximilian, Petry, Andreas, Görlach, Agnes, Husse, Britta, Franz, Wolfgang-Michael, and Zaruba, Marc-Michael
- Subjects
HYDROXYLASE inhibitors ,LEUCOCYTES ,CORONARY disease ,ENDOTHELIAL cells ,BONE marrow - Abstract
SDF-1/CXCR4 activation facilitates myocardial repair. Therefore, we aimed to activate the HIF-1α target genes SDF-1 and CXCR4 by dimethyloxalylglycine (DMOG)-induced prolyl-hydroxylase (PH) inhibition to augment CXCR4+ cell recruitment and myocardial repair. SDF-1 and CXCR4 expression was analyzed under normoxia and ischemia ± DMOG utilizing SDF-1-EGFP and CXCR4-EGFP reporter mice. In bone marrow and heart, CXCR4-EGFP was predominantly expressed in CD45+/CD11b+ leukocytes which significantly increased after myocardial ischemia. PH inhibition with 500 μM DMOG induced upregulation of SDF-1 mRNA in human microvascular endothelial cells (HMEC-1) and aortic vascular smooth muscle cells (HAVSMC). CXCR4 was highly elevated in HMEC-1 but almost no detectable in HAVSMC. In vivo, systemic administration of the PH inhibitor DMOG without pretreatment upregulated nuclear HIF-1α and SDF-1 in the ischemic mouse heart associated with increased recruitment of CD45+/CXCR4-EGFP+/CD11b+ cell subsets. Enhanced PH inhibition significantly upregulated reparative M2 like CXCR4-EGFP+ CD11b+/CD206+ cells compared to inflammatory M2-like CXCR4-EGFP+ CD11b+/CD86+ cells associated with reduced apoptotic cell death, increased neovascularization, reduced scar size, and an improved heart function after MI. In summary, our data suggest increased PH inhibition as a promising tool for a customized upregulation of SDF-1 and CXCR4 expression to attract CXCR4+/CD11b+ cells to the ischemic heart associated with increased cardiac repair. Key messages: [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
4. Differential transcriptional regulation of hypoxia-inducible factor-1α by arsenite under normoxia and hypoxia: involvement of Nrf2.
- Author
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Al Taleb, Zukaa, Petry, Andreas, Chi, Tabughang, Mennerich, Daniela, Görlach, Agnes, Dimova, Elitsa, and Kietzmann, Thomas
- Subjects
HYPOXIA-inducible factor 1 ,SODIUM arsenite ,MITOGEN-activated protein kinase regulation ,REACTIVE oxygen species ,NADPH oxidase - Abstract
Arsenite (As(III)) is widely distributed in nature and can be found in water, food, and air. There is significant evidence that exposure to As(III) is associated with human cancers originated from liver, lung, skin, bladder, kidney, and prostate. Hypoxia plays a role in tumor growth and aggressiveness; adaptation to it is, at least to a large extent, mediated by hypoxia-inducible factor-1α (HIF-1α). In the current study, we investigated As(III) effects on HIF-1α under normoxia and hypoxia in the hepatoma cell line HepG2. We found that As(III) increased HIF-1α protein levels under normoxia while the hypoxia-mediated induction of HIF1α was reduced. Thereby, the As(III) effects on HIF-1α were dependent on both, transcriptional regulation via the transcription factor Nrf2 mediated by NOX4, PI3K/Akt, and ERK1/2 as well as by modulation of HIF-1α protein stability. In line, the different effects of As(III) via participation of HIF-1α and Nrf2 were also seen in tube formation assays with endothelial cells where knockdown of Nrf2 and HIF-1α abolished As(III) effects. Overall, the present study shows that As(III) is a potent inducer of HIF-1α under normoxia but not under hypoxia which may explain, in part, its carcinogenic as well as anti-carcinogenic actions. Key message: [ABSTRACT FROM AUTHOR]
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- 2016
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- View/download PDF
5. Tissue inhibitor of metalloproteinases-1-induced scattered liver metastasis is mediated by hypoxia-inducible factor-1α.
- Author
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Schelter, Florian, Halbgewachs, Birgit, Bäumler, Petra, Neu, Caroline, Görlach, Agnes, Schrötzlmair, Florian, and Krüger, Achim
- Abstract
The 'protease web', representing the network of proteases, their inhibitors, and effector molecules, arises as a pivotal determinant of tissue homeostasis. Imbalances of this network, for instance caused by elevated host levels of tissue inhibitor of metalloproteinases-1 (TIMP-1), have been shown to increase the susceptibility of target organs to scattered metastasis by inducing the hepatocyte growth factor (HGF) pathway. Increased expression of the hypoxia-inducible factor-1α-subunit (HIF-1α) is also associated with tumour progression and is also known to induce HGF-signaling via up-regulation of the HGF-receptor Met, namely under canonical stress conditions like lack of oxygen. Here, we aimed to identify a possible metastasis-promoting connection between TIMP-1, HIF-1α, and HGF-signaling. We found that HIF-1α and HIF-1-signaling were increased during liver metastasis of L-CI.5s T-lymphoma cells in TIMP-1 overexpressing syngeneic DBA/2 mice. In vitro, exposure of L-CI.5s cells to recombinant TIMP-1 revealed that TIMP-1 itself was able to induce HIF-1α and HIF-1-signaling. Knock-down of HIF-1α identified tumour cell-derived HIF-1α as mediator of this TIMP-1-induced invasiveness in vitro. In vivo, HIF-1α knock-down significantly impaired Met expression as well as Met phosphorylation and inhibited scattered liver metastasis. Furthermore, HGF-dependent TIMP-1-promoted Met phosphorylation and HGF-dependent TIMP-1-induced invasiveness in vitro was mediated by HIF-1α. We conclude that elevated levels of TIMP-1 in the microenvironment of tumour cells can promote metastasis by inducing HIF-1α-dependent HGF-signaling. This connection between a protease inhibitor (TIMP-1) and a classically stress-related factor (HIF-1α) is a so far undiscovered impact of the 'protease web' on tissue homeostasis with important implications for metastasis. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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6. SGK1-dependent cardiac CTGF formation and fibrosis following DOCA treatment.
- Author
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Vallon, Volker, Wyatt, Amanda W., Klingel, Karin, Dan Yang Huang, Hussain, Azeemudeen, Berchtold, Susanne, Friedrich, Björn, Grahammer, Florian, BelAiba, Rachida S., Görlach, Agnes, Wulff, Peer, Daut, Jürgen, Dalton, Nancy D., Ross Jr., John, Flögel, Ulrich, Schrader, Jürgen, Osswald, Hartmut, Kandolf, Reinhard, Kuhl, Dietmar, and Lang, Florian
- Subjects
HEART fibrosis ,GROWTH factors ,ALDOSTERONE ,MINERALOCORTICOIDS ,ADRENOCORTICAL hormones ,THERAPEUTICS - Abstract
The mineralocorticoids aldosterone and deoxycorticosterone acetate (DOCA) stimulate renal tubular salt reabsorption, increase salt appetite, induce extracellular volume expansion, and elevate blood pressure. Cardiac effects of mineralocorticoids include stimulation of matrix protein deposition leading to cardiac fibrosis, which is at least partially due to the direct action of the hormones on cardiac cells. The signaling mechanisms mediating mineralocorticoid-induced cardiac fibrosis have so far remained elusive. Mineralocorticoids have been shown to upregulate the serum- and glucocorticoid-inducible kinase 1 (SGK1), which participates in the effects of mineralocorticoids on renal tubular Na
+ reabsorption and salt appetite. To explore the involvement of SGK1 in the pathogenesis of mineralocorticoid-induced cardiac fibrosis, SGK1 knockout mice ( sgk1−/− ) and wild-type littermates ( sgk1+/+ ) were implanted a 21-day-release 50-mg DOCA pellet and supplied with 1% NaCl in drinking water for 18 days. This DOCA/high-salt treatment increased blood pressure in both genotypes but led to significant cardiac fibrosis only in sgk1+/+ but not in sgk1−/− mice. According to real-time polymerase chain reaction and Western blotting, DOCA/high-salt treatment enhanced transcript levels and protein expression of cardiac connective tissue growth factor (CTGF) only in sgk1+/+ but not in sgk1−/− mice. Furthermore, DOCA (10 μM) upregulated CTGF expression and enhanced CTGF promoter activity in lung fibroblasts isolated from sgk1+/+ but not from sgk1−/− mice, an effect involving spironolactone-sensitive mineralocorticoid receptors and activation of nuclear factor-κB (NFκB). Our results suggest that SGK1 plays a decisive role in mineralocorticoid-induced CTGF expression and cardiac fibrosis. [ABSTRACT FROM AUTHOR]- Published
- 2006
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7. Volumetric optoacoustic tomography enables non-invasive in vivo characterization of impaired heart function in hypoxic conditions.
- Author
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Ivankovic, Ivana, Deán-Ben, Xose Luis, Lin, Hsiao-Chun Amy, Zhang, Zuwen, Trautz, Benjamin, Petry, Andreas, Görlach, Agnes, and Razansky, Daniel
- Abstract
Exposure to chronic hypoxia results in pulmonary hypertension characterized by increased vascular resistance and pulmonary vascular remodeling, changes in functional parameters of the pulmonary vasculature, and right ventricular hypertrophy, which can eventually lead to right heart failure. The underlying mechanisms of hypoxia-induced pulmonary hypertension have still not been fully elucidated while no curative treatment is currently available. Commonly employed pre-clinical analytic methods are largely limited to invasive studies interfering with cardiac tissue or otherwise ex vivo functional studies and histopathology. In this work, we suggest volumetric optoacoustic tomography (VOT) for non-invasive assessment of heart function in response to chronic hypoxia. Mice exposed for 3 consecutive weeks to normoxia or chronic hypoxia were imaged in vivo with heart perfusion tracked by VOT using indocyanide green contrast agent at high temporal (100 Hz) and spatial (200 µm) resolutions in 3D. Unequivocal difference in the pulmonary transit time was revealed between the hypoxic and normoxic conditions concomitant with the presence of pulmonary vascular remodeling within hypoxic models. Furthermore, a beat-to-beat analysis of the volumetric image data enabled identifying and characterizing arrhythmic events in mice exposed to chronic hypoxia. The newly introduced non-invasive methodology for analysis of impaired pulmonary vasculature and heart function under chronic hypoxic exposure provides important inputs into development of early diagnosis and treatment strategies in pulmonary hypertension. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
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