A5035875917- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Viral Infections and Immunology Research
- RNA regulation and disease
- RNA modifications and cancer
- Cardiac Fibrosis and Remodeling
- Inflammasome and immune disorders
- Transplantation: Methods and Outcomes
- Cardiovascular Effects of Exercise
- Cardiomyopathy and Myosin Studies
- Circular RNAs in diseases
- Immune Response and Inflammation
- GDF15 and Related Biomarkers
- Extracellular vesicles in disease
- Atherosclerosis and Cardiovascular Diseases
- Kawasaki Disease and Coronary Complications
- Cardiovascular Health and Risk Factors
- Mycobacterium research and diagnosis
- High Altitude and Hypoxia
- Chronic Obstructive Pulmonary Disease (COPD) Research
- MicroRNA in disease regulation
- Muscle Physiology and Disorders
- RNA and protein synthesis mechanisms
- Cardiac Valve Diseases and Treatments
- Exercise and Physiological Responses
University Hospital Leipzig
2021-2024
Klinik und Poliklinik für Neurologie
2022-2024
Leipzig University
2021
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.
Background: Cardiogenic shock (CS) is characterized by impaired cardiac function, very high mortality, and limited treatment options. The pro-inflammatory signalling during different phases of CS incompletely understood. Methods: We collected serum plasma (N=44) as well freshly isolated peripheral blood mononuclear cells (PBMC, N=7) patients with complicating acute myocardial infarction on admission after revascularization (24h, 48h, 72h) healthy controls (serum N=75; PBMC N=12). Results:...
Objectives: The intracellular NLRP3 inflammasome is an important regulator of sterile inflammation. Recent data suggest that particles can be released into circulation. effects exercise on circulating extracellular apoptosis-associated speck-like protein (ASC) and their endothelial cells are not known. Methods: We established a flow cytometric method to quantitate ASC specks in human serum. were quantitated 52 marathon runners 24-72 h before, immediately after, again 24-58 after the run. For...
Abstract To adapt to changing hemodynamic demands, regulatory mechanisms modulate actin-myosin-kinetics by calcium-dependent and -independent mechanisms. We investigate the posttranslational modification of human essential myosin light chain (ELC) identify NIMA-related kinase 9 (NEK9) interact with ELC. NEK9 is highly expressed in heart interaction ELC calcium-dependent. Silencing results blunting ELC-phosphorylation. CRISPR/Cas9-mediated disruption leads cardiomyopathy zebrafish. Binding...
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...
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...
Abstract Cardiogenic shock (CS) still has a mortality rate of approximately 50%. CS leads to significant activation the immune system. The aim this study was characterize cell populations and cell-specific changes in on admission clinic after revascularization. We developed web-based platform named 'IRCaS - Immune Cell Regulations Shock' map temporal course processes acute myocardial infarction (AMI) from 3 days Our tool revealed an endogenous anti-inflammatory response CS, which is...
Abstract Background and purpose Cardiogenic shock (CS) remains the leading cause of death in acute myocardial infarction (AMI), with high mortality rates 40–50%. The long non-coding RNA (lncRNA) Heat4 is associated inflammatory response non-classical monocytes. Previous experimental work shows that this mechanism may be important heart failure (HF) during regeneration after vascular injury. Here, we investigate association survival patients chronic HF assessed its regulation AMI CS. Methods...
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...
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 Activation of the immune system correlates with severity prognosis patients heart failure (HF). Here, we aim to identify characterize long non-coding RNAs (lncRNAs) as a potential mechanistic link between activation pathophysiology HF. Methods results Using next-generation sequencing found yet uncharacterized lncRNA be significantly upregulated in peripheral blood mononuclear cells ischemic cardiomyopathy compared controls, which named Heat4 – Heart-disease...
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 Objectives The intracellular NLRP3 inflammasome is an important regulator of sterile inflammation. Recent data suggest that particles can be released into the circulation. effects exercise on circulating extracellular apoptosis-associated speck-like protein (ASC) and their endothelial cells are not known. Methods We established a flow cytometric method to quantitate ASC specks in human serum. were quantitated 52 marathon runners 24–72 hours before, immediately after, again 24–58...
Abstract Background and purpose Activation of the immune system correlates with severity prognosis patients heart failure (HF). This study aims to identify characterize long non-coding RNAs (lncRNAs) as a potential mechanistic link between pathophysiology HF activation system. Methods results Next-generation sequencing (NGS) studies identified 2.05-fold increase lncRNA Heat4 in blood compared controls, which was validated larger cohort (HF: N=63; Controls: N=38; p<0.05)....
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....
Background and Purpose: Activation of the immune system correlates with severity prognosis patients heart failure (HF). This study aims to identify characterize long non-coding RNAs (lncRNAs) as a potential mechanistic link between pathophysiology HF activation system. Methods Results: Using next-generation sequencing, we identified lncRNA Heat4 be 2-fold upregulated in blood compared controls (N=4; p<0.05). induction was validated an independent second patient cohort via qPCR (HF: N=63;...
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...