Experimental Immunocardiology

Our research is focused at exploring the role of the innate and adaptive immunity in the pathogenesis of non-ischemic heart failure with main interest in inflammatory cardiomyopathy and heart failure with preserved ejection fraction. The relevance of extra-cardiac versus cardiac inflammation on the pathogenesis of heart failure is investigated. In addition, our research is directed at the search for novel therapeutic targets as well as the evaluation of repurposed anti-inflammatory and immunomodulatory strategies.

In view of translational research, patient materials of specific heart failure cohorts are analyzed and identified targets and therapies evaluated in experimental models.

NLRP3 inflammasome and S100A8/A9 alarmins
(cardiac) fibroblasts as inflammatory supporter cells
cardiosplenic axis
immunometabolism
immune checkpoint inhibitors and myocarditis
immunomodulating strategies: cell-based and pharmacological strategies

https://www.ncbi.nlm.nih.gov/pubmed/?term=van+linthout+s
The Quest for antiinflammatory and immunomodulatory strategies in heart failure:
addressing the need for translational preclinical models, refined approaches and stratification of patients.
https://www.ncbi.nlm.nih.gov/pubmed/31544235
Mode-of-action of the PROPELLA concept in fulminant myocarditis:
describing how prolonged left ventricle unloading via an axilliary pump as mechanical circulatory support, is associated with disease-modifying effects.
https://www.ncbi.nlm.nih.gov/pubmed/30891599
Cardiac (myo)fibroblasts modulate the migration of monocyte subsets:
describing how (myo)fibroblasts depending on the inflammatory environment, secrete specific chemokines, affecting the migration of pro- versus anti-inflammatory monocytes. https://www.ncbi.nlm.nih.gov/pubmed/29615815
Inflammation - cause or consequence of heart failure or both?:
adressing how inflammation and heart failure are strongly interconnected and mutually reinforce each other.
https://www.ncbi.nlm.nih.gov/pubmed/28667492
Dr. rer. nat. Dipl.-Pharm. Kathleen Pappritz
Phone: +49-(0)30- 450 539 456 or 509
Email: kathleen.pappritz@charite.de
Dr. rer. nat. Irene Müller
Phone: +49-(0)30 450 539 456 or 509
Email: Irene.mueller@charite.de
Dr. rer. nat. Dipl.-Biol. Muhammad El-Shafeey
Phone: +49-(0)30- 450 539 456
Email: Muhammad.EL-Shafeey@charite.de
Dipl.-Ing. Annika Koschel, Technician
Phone: +49-(0)30 450 539 456 or 509
Email: annika.koschel@charite.de
Kerstin Puhl, Technician
Phone: +49-(0)30- 450 539 536
Email: kerstin.puhl@charite.de
Marzena Sosnowski, Technician
Phone: +49-(0)30- 450 539 456 or 509
Email: marzena.sosnowski@charite.de
Patient material
Characterization of endomyocardial biopsies:
via immunohistochemistry, gene expression analysis, flow cytometry and outgrowth culture of cardiac fibroblasts
Characterization of transcoronary gradients via flow cytometry
Identification of circulating fibrocytes, (apoptotic) endothelial cells, mononuclear cell subsets via flow cytometry

Cell isolation, culture and in vitro models
Human cell isolation: endomyocardial biopsy-derived fibroblasts and mononuclear cells and peripheral blood mononuclear cells (PBMCs)
Murine cell isolation: left ventricle-, right ventricle-, muscle-derived and cancer-associated fibroblasts, cardiac mononuclear cells, endothelial cells, splenocytes, PBMCs
Cell culture: mesenchymal stromal cells (MSCs), HUVEC, HAEC, HL-1 cardiomyocytes, THP-1 cells, fibroblasts
Co-cultures
Stress models:
coxsackievirus B3 (CVB3)-, parvovirus B19-, hyperglycemia-, angiotensin II-, tumor necrosis factor-α-, interferon-g, transforming growth factor-ß-induced stress

Animal models and functional measurements
Animal models:
CVB3-induced inflammatory cardiomyopathy, myocardial infarction, diabetic cardiomyopathy, angiotensin II-induced heart failure
Left ventricular function:
conductance catheter and echocardiography, including strain analysis via speckle-tracking echocardiography
Endothelial function:
organ water bath method

Sophie van Linthout

Patient material

Cell isolation, culture and in vitro models

Animal models and functional measurements

Experimental Immunocardiology

Sophie van Linthout

Publications

Team

Methods