A5010358942- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- RNA regulation and disease
- Viral Infections and Immunology Research
- Epigenetics and DNA Methylation
- GDF15 and Related Biomarkers
- Immune cells in cancer
- Circular RNAs in diseases
- MicroRNA in disease regulation
- Cardiovascular Health and Risk Factors
- Atherosclerosis and Cardiovascular Diseases
- Congenital heart defects research
- Cardiomyopathy and Myosin Studies
- Immune Response and Inflammation
- Inflammatory Biomarkers in Disease Prognosis
- Nuclear Structure and Function
- Cardiac Fibrosis and Remodeling
- RNA and protein synthesis mechanisms
University Hospital Leipzig
2018-2024
Klinik und Poliklinik für Neurologie
2020-2024
Leipzig University
2021
St. Elisabeth-Krankenhaus Leipzig
2021
Endothelial cells play an important role in maintenance of the vascular system and repair after injury. Under proinflammatory conditions, endothelial can acquire a mesenchymal phenotype by process named endothelial-to-mesenchymal transition (EndMT), which affects functional properties cells. Here, we investigated epigenetic control EndMT. We show that histone demethylase JMJD2B is induced EndMT-promoting, proinflammatory, hypoxic conditions. Silencing reduced TGF-β2-induced expression genes,...
Abstract Alterations of RNA editing that affect the secondary structure RNAs can cause human diseases. We therefore studied in failing hearts. Transcriptome sequencing showed adenosine-to-inosine (A-to-I) was responsible for 80% events myocardium. Failing hearts were characterized by reduced editing. This primarily attributable to Alu elements introns protein-coding genes. In left ventricle, 166 circRNAs upregulated and 7 downregulated compared non-failing controls. Most associated with host...
Lipodystrophy syndromes (LDs) are characterized by loss of adipose tissue, metabolic complications such as dyslipidemia, insulin resistance, and fatty liver disease, well accelerated atherosclerosis. As a result tissue deficiency, the systemic concentration adipokine leptin is reduced. A current promising therapeutic option for patients with LD treatment recombinant (metreleptin), resulting in reduced risk mortality. Here, we investigate effects on endothelial to mesenchymal transition...
Alternative mRNA splicing is a fundamental process to increase the versatility of genome. In humans, cardiac involved in pathophysiology heart failure. Mutations factor RNA binding motif protein 20 (RBM20) cause severe forms cardiomyopathy. To identify novel cardiomyopathy-associated factors, RNA-seq and tissue-enrichment analyses were performed, which identified up-regulated expression Sam68-Like mammalian 2 (SLM2) left ventricle dilated cardiomyopathy (DCM) patients. human heart, SLM2...
Activation of the immune system contributes to cardiovascular diseases. The role human-specific long noncoding RNAs in cardioimmunology is poorly understood.
Abstract Background The mortality rate of cardiogenic shock (CS) is around 50%. There a need for biomarkers to predict the prognosis CS. Due their shape, circular RNAs (circRNAs) exhibit higher stability than other classes RNA. Regulation circRNAs has been observed in cardiovascular diseases such as myocardial infarction, but regulation CS largely unknown. Monocytes can be classified into different populations based on surface markers. Non-classical and intermediate monocytes are...
Introduction: Trimethylamine N-oxide (TMAO) derived from dietary sources has been linked to a higher risk of atherosclerotic disease. However, the underlying mechanisms are not fully understood. Impairment endothelial cells (ECs) by chronic inflammation or metabolic cues can lead loss EC phenotype and function towards mesenchymal cell type, process contributing atherosclerosis termed endothelial-to-mesenchymal transition (EndMT). Here, we investigate potential uptake TMAO its impact on...
Introduction: The versatility of the human genome is increased by process alternative mRNA splicing. Impaired splicing cardiac transcriptome involved in pathophysiology heart failure. Especially, mutations cardiac-specific factors such as RBM20 cause severe forms cardiomyopathy. Aim: We aimed to identify novel cardiomyopathy-associated using a score myocardial tissue specificity including 53 tissues and disease-associated expression changes hearts dilated cardiomyopathy (DCM) patients...
Endothelial-to-mesenchymal transition (EndMT) is triggered by stress stimuli and characterized the conversion of endothelial cells (EC) into mesenchymal cells. Stress such as hypoxia or inflammation depend on rapid gene expression mediated RNA elongation. elongation controlled super complex (SEC) through transient pausing Polymerase II (RNAPII). We aimed to analyze regulatory role during onset EndMT. In an in vitro EndMT model, SEC scaffolds AFF1 AFF4 were upregulated compared controls....
Abstract Background Endothelial dysfunction is characterized by endothelial-to-mesenchymal transition (EndMT), a process in which endothelial cells (EC) transform into mesenchymal and lose part of their identity. EndMT-positive are present vulnerable atherosclerotic plaques. EndMT triggered stress stimuli such as inflammation or hypoxia that require an adaptive change gene expression mediated at the level RNA elongation. elongation controlled super complex (SEC), built around scaffolding...
Abstract Introduction and Purpose Growth Differentiation Factor 15 (GDF15) is a member of the TGF-β superfamily upregulated under conditions injury stress such as hypoxia. GDF15 serum concentrations correlate with inflammation, cardiac fibrosis unfavorable prognosis in cardiovascular diseases. The functional role endothelial cells largely unknown. Here, we investigate possible transdifferentiation (EC) into mesenchymal (EndMT). Methods Results expressed at mRNA protein level primary human...
Abstract Background and purpose Adenosine-to-Inosine (A-to-I) RNA editing is a post-transcriptional modification process that affects the secondary structure of RNAs. Changes in have been associated with human diseases. We therefore aimed to analyze healthy failing heart. Methods results Transcriptome sequencing heart samples failure (HF) patients (n=20) controls (n=10) revealed A-to-I as major type (>80%). In HF patients, was reduced, which primarily attributable Alu elements introns...
Abstract Background and purpose EndMT describes a process in which endothelial cells lose their features such as the maintenance of vascular barrier function trans-differentiate into mesenchymal like cells. ECs have underwent are enriched vulnerable plaques humans. Several stress stimuli hypoxia or inflammation demand immediate induction adaptive gene expression to improve cell survival. In contrast usual requires several hours, release paused RNA Polymerase II (RNAPII) from promoter allows...
Abstract Background and purpose Trimethylamine N-oxide (TMAO) is associated with a higher risk of atherosclerotic diseases. However, the underlying molecular mechanisms are not completely understood. Inflammation following endothelial-to-mesenchymal transition (EndMT) – process where endothelial cells (ECs) lose their function phenotype gain mesenchymal character contribute to development atherosclerosis. We therefore aimed investigate potential uptake TMAO into ECs its impact on...
Abstract Background and purpose Post-transcriptional RNA editing is an important mechanism in the development of human diseases. can affect stability alternative splicing. The aim our study was to characterize its impact on splicing healthy failing heart. Methods results Human heart samples failure (HF) patients (n=20) controls (n=10) were analyzed using sequencing with subsequent analysis editing. We identified adenosine-to-inosine (A-to-I) as major form hearts, being reduced HF patients....
Introduction: Adenosine-to-Inosine (A-to-I) RNA editing is a post-transcriptional modification process regulating stability and alternative splicing. A-to-I conducted by the enzymes ADAR1 ADAR2 mainly targets Alu elements, primate-specific elements which have been associated with formation of circular (circRNA). Although differential expression circRNAs has studied in heart failure (HF), extent consequences human remain largely unknown. Methods Results: We analyzed samples HF (n=20) patients...