Klinik für Kardiologie
 
Arbeitsgruppen
 
Klinik für Kardiologie / Forschung
 
 
Research Lab
 
The Heart Center Leipzig has a strong expertise in clinical research and is committed to the continuous improvement of patient care and intervention.
The knowledge on pathomechanisms that underpin the development of heart diseases is still limited. We therefore carry out various projects in the area of basic research and clinical research in order to make a contribution to scientific progress.
 
Members of the group and associated physicians and scientists

Petra Büttner, PhD
Julia Böttner, PhD
Sarah Werner (MTA)
Reena Prajapati
Wenke Cheng

Former group members:

Paulien Vinke, MSc
Florian Schlotter, MD
Danilo Obradovic, MD
Jelena Kornej, MD, MSc
Laura Ueberham, MD
Sophia Eisenkolb, MD
Tina Fischer-Scheapmann (MTA)
Sarah Knauth (MTA)

Head of Lab: Petra Büttner

Research interests: biology of cardiomyocytes, heart failure, atrial fibrillation, HDL-dysfunction, biomarkers in acute myocardial infarction with cardiogenic shock, biomarkers in atrial fibrillation
 
Biomarkers in acute myocardial infarction and cardiogenic shock

Coronary artery disease is the single most frequent cause of death accounting for 13% of all deaths. Every sixth man and every seventh woman in Europe will die from myocardial infarction. Despite ongoing improvement of therapeutically reperfusion approaches mortality remains substantial with approximately 12% of patients dead within 6 months. These facts justify continuous efforts to improve quality of care, adherence to guidelines and research. The pathomechanisms that underpin the decay of the myocardium in acute myocardial infarction include ischemia reperfusion injury following characterized by increased oxidative stress, inflammation and ultimately death of myocardial tissue which may be of particular importance in infarct-related cardiogenic shock.
  • doi: 10.1097/SHK.0000000000001342
  • doi: 10.1093/eurheartj/ehab110
  • doi: 10.1093/eurheartj/ehab110
  • doi: 10.3390/jcm11237168
 
Regulatory Function of Biomarkers in the Context of Cardiogenic Shock - Project led by Reena Prajapati

Biomarkers related to cardiogenic shock demonstrate distinct kinetic profiles, indicative of their modulation by diverse cellular responses. A comprehensive understanding of these underlying pathomechanisms serves as an essential foundation for enhancing therapeutic options for afflicted patients.
We are particularly interested in characterizing the inflammatory reaction of endothelial cells in response to molecular patterns associated with cardiogenic shock. This study focuses on the impact of CS-linked circulating biomarkers on multiple cellular components, encompassing endothelial cells, cardiomyocytes, hepatocytes, skeletal myocytes, renal cells, and the neural system. The integration of all four CLIP parameters is proposed to be conducted within hypoxic conditions. Moreover, a meticulous examination is undertaken to decipher the regulatory miRNAs targeted by IL-6 and other CLIP markers in the cohort of cardiogenic shock patients. The validation of these findings is intended through the application of bioinformatics tools.
 
Methamphetamine Induced Heart Failure - Project led by Dr. Julia Böttner

Methamphetamine as a substance of the amphetamine type acts primarily in the central nervous system (CNS). It is more lipophilic than its metabolites and can therefore easily cross the blood-brain barrier. The release of catecholamines, such as epinephrine, dopamine, and serotonin, with concomitant inhibition of their reuptake, is well studied as a major mechanism of psychoactivity. Characterization of a cohort from the Leipzig Heart Center showed that young patients have cardiac pathologies after regular use of meth. These pathologies range from hypertension to arrhythmias, vasospasm, cardiomyopathies to accelerated arteriosclerosis, vascular dissections and sudden cardiac death. Central nervous stimulated catecholamine action is discussed as the cause of the observed cardiotoxicity, but also direct damage to myocardial or other cells. Whether catecholamines or direct effects on myocardium and vasculature are the cause of the meth-associated cardiac injury requires further research.
Identification of molecular targets and drug-induced signal transduction is beyond dispute linking their known damaging effects to subcellular key players following drug - driven alternative signaling. Therefore, adverse effects of meth on endothelial and cardiac cells are monitored using impedance spectroscopy in real-time. The involvement of proteinkinase C, protein phosphatase 2A, endothelial NO synthase as well as von Willebrand factor, endothelin and inflammatory signaling are investigated on gene and protein expression levels.
The understanding of meth-induced intracellular signaling will lead to improved treatment of cardiac events among patients following meth abuse.
 
Heart failure with preserved ejection fraction - Lessons from an animal model

Heart failure with preserved ejection fraction (HFpEF) is associated with high morbidity and mortality yet there are no evidence-based therapies. Obese ZSF1 rats spontaneously develop hypertension, hyperlipidemia and glucose intolerance and finally HFpEF and thus offer the possibility to study underpinning pathomechanisms. We currently analyze inflammatory infiltration of the heart, alterations in the gut-heart axis and alterations in cardiomyocytes cytoskeleton using this animal model. In humans arterial stiffness on the left ventricle and impaired endothelial function are discussed as potential causative factors of HFpEF and point towards an imbalance of nitric oxide (NO) metabolism. NO metabolizing enzymes depend on arginine and its derivatives. Thus, the analysis of the arginine metabolism is in the focus of current experiments.
  • doi: 10.1038/s41598-022-19766-5
  • doi: 10.1002/ehf2.14110
  • doi: 10.1007/s00726-021-03042-3
  • doi: 10.1038/s41598-021-00216-7
 
Clonal Hematopoiesis in cardiovascular disease

In collaboration with partners from different institutions of the University of Leipzig such as the Institute of Laboratory Medicine, the Leipzig Medical Biobank, the Department of Hematology, Cellular Therapy and Hemostaseology, the Core Unit DNA-Technologies and the Visceral, Transplantation, Thorax and Vascular Surgery at the Medical Faculty at University of Leipzig, we investigated associations of clonal hematopoiesis (CH) mutations with cardiovascular disease. We found that CH mutations predict mortality in cardiogenic shock and showed for the first time that CH mutations are present not only in circulating blood cells but also in atherosclerotic lesions in peripheral artery disease.
  • doi: 10.3390/ijms24043962
  • doi: 10.1007/s00395-022-00969-w
 
Biomarkers of atrial fibrillation progression

The identification and characterization of atrial fibrillation progression surrogate markers has the potential to significantly improve the suitability of established clinical risk scores for atrial fibrillation recurrence prediction. We hope that in the future combined use of clinical scores and biomarkers will be used for therapeutic stratification and monitoring in atrial fibrillation. This project is in close collaboration with PD Dr. med. MSc Jelena Kornej from Boston University School of Medicine.
  • doi: 10.1371/journal.pone.0198461
  • doi: 10.1016/j.hrthm.2018.03.021
  • doi: 10.1093/europace/euy120
  • doi: 10.1016/j.ijcha.2020.100554. eCollection 2020 Aug
  • doi: 10.1007/s00109-020-01932-9
  • doi: 10.1007/s00392-019-01512-z
  • doi: 10.1007/s10840-021-01020-z
 
HDL-dysfunction in Atrial Fibrillation

Increased morbidity and mortality in atrial fibrillation (AF) are related to the pro-fibrotic, pro-thrombotic and pro-inflammatory processes that underpin the disease. High-density lipoproteins (HDL) have anti-inflammatory, anti-oxidative, and anti-thrombotic properties. Functional impairment of HDL may therefore associate with AF initiation or progression. This research project is done in collaboration with the research group of Prof. Gunther Marsche at Otto Loewi Research Center, Medical University of Graz, Austria.
  • doi: 10.1007/s00395-019-0735-0
  • doi: 10.1007/s00380-021-01908-w
 
Genetic background of atrial fibrillation

This project is part of the foundation professorship of Prof. Dr. Daniela Husser-Bollmann (Department of Electrophysiology).
Hundreds or thousands of common genetic variants may modulate atrial fibrillation progression and while each single variant has an almost unmeasurable effect, several single variant effects might sum up and finally have an impact on regulators in the atrial fibrillation pathomechanisms. This hypothesis can be used to identify candidate genes that are associated with AF onset and progression.
From Genetics to Function: Bioinformatical tools give us the opportunity to identify potential new regulators based on the analysis of common genetic variants in the encoding genes for an association with atrial fibrillation phenotypes. The basic assumption is that disease related-genes may be more often than non-related genes affected by genetic variants.
  • doi: 10.3389/fgene.2017.00224
  • doi: 10.1186/s12967-017-1170-3
  • doi: 10.1371/journal.pone.0167008
  • doi: 10.1038/srep36630
  • doi: 10.3389/fgene.2018.00162
 
Innovation

We aim for the ongoing implementation of novel technologies and methods to broaden our scientific spectrum. This enables interesting new insights into cardiovascular pathomechanisms.

We identified an association of circulating EGF-receptor ligands (HB-EGF and EGF) with atrial fibrillation based on genetic evidence.
  • doi: 10.1161/CIRCEP.119.007212

Nonlinear optical microscopy (NLOM) is an immediate, non-destructive method to visualize and characterize in detail AF associated remodeling. For this purpose, we applied coherent anti-Stokes Raman scattering (CARS), endogenous two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) to inspect unstained human atrial appendage myocardium ex vivo. As such, ambitious development of in vivo application of the NLOM technique may represent a revolutionary approach in characterizing myocardial tissue characteristics. This study was done in cooperation with Dr. Roberta Galli form the research group Clinical Sensoring and Monitoring at the TU Dresden.
  • doi: 10.4022/jafib.1644
 
Julia Böttner
Methamphetamine Induced Heart Failure

Reena Prajapati


Aktuelles
 
 22.02.2024 - 24.02.2024
16. Deutsche Kardiodiagnostik-Tage
 
 
 22.03.2024 - 23.03.2024
Kardiovaskuläre Frühjahrstagung
 
 
Klinik für Kardiologie