Decrease in dendritic cells in endomyocardial biopsies of human dilated cardiomyopathy
Rudin Pistulli1, Sebastian König, Stefanie Drobnik
1Clinic of Internal Medicine I, Division of Cardiology and Intensive Care Medicine, University Hospital of Jena, Germany. rudin.pistulli@med.uni-jena.de
Insights
Dendritic cells (DCs) are significantly reduced in the heart muscle of patients with dilated cardiomyopathy (DCM). This DC deficiency is linked to poorer heart function and may stem from tissue damage and poor vascularization in heart failure.
Area of Science:
- Immunology
- Cardiology
- Pathology
Background:
- Dendritic cells (DCs) are crucial immune sentinels.
- Their role in myocardial disease, specifically dilated cardiomyopathy (DCM), remains largely unknown.
- Investigating DC presence in DCM is vital for understanding cardiac immune responses.
Purpose of the Study:
- To investigate the presence and characteristics of dendritic cells (DCs) within the myocardium of human dilated cardiomyopathy (DCM) patients.
- To correlate DC levels with disease severity, fibrosis, apoptosis, and clinical outcomes.
Main Methods:
- Immunohistochemical analysis of endomyocardial biopsies from 72 DCM patients and 18 controls.
- Quantification of DCs, antigen-presenting cells (APCs), T cells, macrophages, fibrosis, and apoptosis.
- Polymerase chain reaction for viral genomes and clinical follow-up for ejection fraction (EF) changes.
Main Results:
- Myocardial DCs (all subtypes and maturation stages) were significantly decreased in DCM patients compared to controls.
- Regulatory T cells and apoptosis markers were overexpressed in DCM.
- Reduced DCs correlated with endothelial progenitor cells, increased fibrosis, and inversely with ejection fraction change.
Conclusions:
- Symptomatic DCM patients exhibit reduced myocardial dendritic cells (DCs).
- This DC reduction is associated with unfavorable short-term outcomes, including decreased ejection fraction.
- Potential causes include myocardial tissue damage, cellular death, and insufficient vascularization in chronic heart failure.
Aims:
Dendritic cells (DCs) are sentinels of the immune system-their role in myocardial disease is unknown as yet. We investigated their myocardial presence in human dilated cardiomyopathy (DCM).
Methods And Results:
Endomyocardial biopsies from 72 patients with DCM (EF ∼30%), as well as myocardial specimens from 18 suicide or accident victims were immunohistochemically analysed for myeloid and plasmacytoid DCs, antigen-presenting cells (APCs), and other leucocytes; also tissue fibrosis and apoptosis were histologically quantified. The myocardial viral genome was identified through polymerase chain reaction, and patients underwent clinical follow-up in 3-6 months. We found myocardial DCs of all examined subtypes and maturation stages (fascin, CD11c, CD209, CD83, and CD304), as well as markers for APCs (HLA-DR and CD40) and T-cell activation (CD69) to be significantly decreased in DCM compared with controls. In contrast, regulatory T cells (the GITR epitope), apoptosis (by TUNEL reaction and immunostaining with BCL-2), and a DC chemokine receptor (CCR7) were overexpressed, while no significant differences were observed for macrophages (CD68). Immature myeloid and plasmacytoid DCs strongly correlated with endothelial progenitor cells (CD34), which were similarly reduced in DCM, and inversely correlated with fibrosis. Myeloid DCs were especially reduced in virus-positive biopsies, and their numbers correlated with positive change in EF (ΔEF) at follow-up.
Conclusion:
Myocardial DCs are reduced in heart biopsies of symptomatic DCM patients. Such a reduction correlates with an unfavourable short-term outcome in terms of EF, and could result from myocardial tissue damage, cellular death, and insufficient vascularization in chronic heart failure.
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