Primary Human Cardiomyocytes and Cardiofibroblasts Treated with Sera from Myocarditis Patients Exhibit an Increased Iron Demand and Complex Changes in the Gene Expression
Kamil A. Kobak,
Paweł Franczuk,
Justyna Schubert,
Magdalena Dzięgała,
Monika Kasztura,
Michał Tkaczyszyn,
Marcin Drozd,
Aneta Kosiorek,
Liliana Kiczak,
Jacek Bania,
Piotr Ponikowski,
Ewa A. Jankowska
Affiliations
Kamil A. Kobak
Laboratory for Applied Research on Cardiovascular System, Department of Heart Diseases, Wroclaw Medical University, 50-556 Wroclaw, Poland
Paweł Franczuk
Laboratory for Applied Research on Cardiovascular System, Department of Heart Diseases, Wroclaw Medical University, 50-556 Wroclaw, Poland
Justyna Schubert
Department of Food Hygiene and Consumer Health Protection, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland
Magdalena Dzięgała
Laboratory for Applied Research on Cardiovascular System, Department of Heart Diseases, Wroclaw Medical University, 50-556 Wroclaw, Poland
Monika Kasztura
Department of Food Hygiene and Consumer Health Protection, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland
Michał Tkaczyszyn
Laboratory for Applied Research on Cardiovascular System, Department of Heart Diseases, Wroclaw Medical University, 50-556 Wroclaw, Poland
Marcin Drozd
Laboratory for Applied Research on Cardiovascular System, Department of Heart Diseases, Wroclaw Medical University, 50-556 Wroclaw, Poland
Aneta Kosiorek
Centre for Heart Diseases, University Hospital, 50-556 Wroclaw, Poland
Liliana Kiczak
Department of Biochemistry and Molecular Biology, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland
Jacek Bania
Department of Food Hygiene and Consumer Health Protection, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland
Piotr Ponikowski
Centre for Heart Diseases, University Hospital, 50-556 Wroclaw, Poland
Ewa A. Jankowska
Laboratory for Applied Research on Cardiovascular System, Department of Heart Diseases, Wroclaw Medical University, 50-556 Wroclaw, Poland
Cardiac fibroblasts and cardiomyocytes are the main cells involved in the pathophysiology of myocarditis (MCD). These cells are especially sensitive to changes in iron homeostasis, which is extremely important for the optimal maintenance of crucial cellular processes. However, the exact role of iron status in the pathophysiology of MCD remains unknown. We cultured primary human cardiomyocytes (hCM) and cardiofibroblasts (hCF) with sera from acute MCD patients and healthy controls to mimic the effects of systemic inflammation on these cells. Next, we performed an initial small-scale (n = 3 per group) RNA sequencing experiment to investigate the global cellular response to the exposure on sera. In both cell lines, transcriptomic data analysis revealed many alterations in gene expression, which are related to disturbed canonical pathways and the progression of cardiac diseases. Moreover, hCM exhibited changes in the iron homeostasis pathway. To further investigate these alterations in sera-treated cells, we performed a larger-scale (n = 10 for controls, n = 18 for MCD) follow-up study and evaluated the expression of genes involved in iron metabolism. In both cell lines, we demonstrated an increased expression of transferrin receptor 1 (TFR1) and ferritin in MCD serum-treated cells as compared to controls, suggesting increased iron demand. Furthermore, we related TFR1 expression with the clinical profile of patients and showed that greater iron demand in sera-treated cells was associated with higher inflammation score (interleukin 6 (IL-6), C-reactive protein (CRP)) and advanced neurohormonal activation (NT-proBNP) in patients. Collectively, our data suggest that the malfunctioning of cardiomyocytes and cardiofibroblasts in the course of MCD might be related to alterations in the iron homeostasis.
