AG Van Linthout: Experimental Immunocardiology

(Deutsche Version folgt)

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



  • The Quest for antiinflammatory and immunomodulatory strategies in heart failure:
    addressing the need for translational preclinical models, refined approaches and stratification of patients.
  • 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.
  • 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.
  • Inflammation - cause or consequence of heart failure or both?:
    adressing how inflammation and heart failure are strongly interconnected and mutually reinforce each other.



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