Phenotypic Patterns of Mononuclear Cells in Dilated Cardiomyopathy

Circulation ◽  
1995 ◽  
Vol 92 (10) ◽  
pp. 2876-2885 ◽  
Author(s):  
Christoph Holzinger ◽  
Andrea Schöllhammer ◽  
Martin Imhof ◽  
Christian Reinwald ◽  
Gero Kramer ◽  
...  
2017 ◽  
Vol 43 (4) ◽  
pp. 1515-1525 ◽  
Author(s):  
Bailing Li ◽  
Wei Zhou ◽  
Xiaojun Tang ◽  
Wei Wang ◽  
Jiajun Pan ◽  
...  

Background/Aims: The imbalance of Treg/Th17 cells plays important role in the pathogenesis of dilated cardiomyopathy (DCM). Response gene to complement (RGC)-32 is a cell cycle regulator that plays an important role in cell proliferation. We evaluated whether the upregulation of RGC-32 was implicated in the homeostasis of Treg/Th17 cells in DCM. Methods: The levels of plasma RGC-32, IL-17 and TGF-β1, and the frequencies of circulating CD4+ RGC-32+ T cells, Th17 and Treg cells in patients with DCM were determined by Cytokine-specific sandwich ELISA and the flow cytometer (FCM), respectively. Results: A significant elevation of plasma RGC-32 in patients with DCM compared with healthy control (HC) subjects was observed. This upregulation was associated with an increase in frequency of Th17 and a decrease in frequency of Treg cells. To further assessed the role of RGC-32, we investigated the effects of RGC-32 up- or down-regulation on frequencies of Th17 and Treg cells in peripheral blood mononuclear cells (PBMCs) from subjects. Importantly, overexpression of RGC-32 was accompanied by an augmentation of Th17 and a reduction of Treg expression. Conclusion: In summary, our study demonstrated the up-regulation of RGC-32 contributed to the imbalance of Treg/Th17 cells in patients with DCM.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Antonio C Campos de Carvalho ◽  
Helena F Martino ◽  
Paulo S Oliveira ◽  
Edmilson Assunção ◽  
Rita Vilela ◽  
...  

Given the limited therapeutic options for refractory dilated cardiomyopathy we decided to perform a phase I clinical trial using bone marrow derived mononuclear cells in patients with functional classes II and IV of the NYHA. Inclusion criteria required EF% (Simpson) <35%, VO2 max < 16 kg.ml /min and signed informed consent. After enrollment patients were subject to the following exams at baseline, 2 and 6 months after cell therapy: 12 lead ECG and 24hs holter, echocardiography, chest X-ray, blood biochemistry, BNP, ergoespirometry, MRI and Minnesota Questionnaire. Patients were subject to bone marrow aspiration (80–100 mL) under sedation and local anesthesia and mononuclear cells were obtained after Ficoll gradient centrifugation. A mean of 198 million cells diluted in 20 ml of saline were slowly delivered through catheterization in the coronary arteries (10 ml in LAD, 5 ml in RC, 5 ml in CX). After the procedure patients remained hospitalized for 48hs. We report the results of the first 22 patients that completed the follow-up period. No adverse effects related to the procedure were observed, nor were arrhythmias detected after cell delivery. Four patients died during follow up. For the 18 patients that completed follow up, there was a significant improvement in NYHA functional class and quality of life at 2 and 6 months (p<0.03 and p< 0.007, respectively). There were no statistically significant changes in EF% (18.6%, 18.6% and 19%), EDV (360, 371, 386 ml) or ESV (295, 308, 314 ml) at baseline, 2 and 6 months respectively as measured by MRI. Maximal oxygen consumption showed as significant increase after cell therapy (12.5, 15.3, 16.8 ml/kg.min), and the number of patients with oxygen consumption below the threshold for cardiac transplantation decrease from 75% at baseline to 25% six months after cell therapy. BNP levels were not significantly altered (650, 475, 530 pg/ml). When observed individually, 4 of the 17 patients examined showed an increase in EF% by MRI ≥5%, 7 did not change EF% and 3 decreased EF% by ≥5%. In conclusion, the procedure is safe and feasible but further studies are necessary to test for efficacy.


2010 ◽  
Vol 21 (1) ◽  
pp. 110-112 ◽  
Author(s):  
Aris Lacis ◽  
Andrejs Erglis

AbstractAlmost half of the children with symptomatic dilated cardiomyopathy receive a transplant or die within 2 years; however, cardiac stem cell transplantation has become a promising therapeutic option. The present case demonstrates for the first time, to our knowledge, the intramyocardial administration of autologous bone marrow mononuclear cells in a critically ill 4-month-old child with severe dilated cardiomyopathy. Left ventricular ejection fraction increased from 20% before stem cell transplantation to 41% at 4 months of follow-up.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Kuemmel ◽  
R Feldtmann ◽  
A Stohbach ◽  
A Riad ◽  
B Chamling ◽  
...  

Abstract Objective Dilated cardiomyopathy (DCM) is characterized by systolic dysfunction and simultaneous dilatation of the left or both ventricles. Besides other causes, the innate immune system plays a major role in the development and progression of the disease. To uncover links between molecular mechanisms and disease progression our group has focused on the toll like receptor 4 / myeloid differentiation factor-2 (MD-2) system. Purpose We already reported that soluble MD-2 (sMD-2) is a risk factor for survival in patients with DCM. High mobility group box protein 1 (HMGB1) is a potent intrinsic interaction partner of MD-2. In the current study, we quantified HMGB-1 in plasma from patients with DCM at baseline, upon first hospital admission. Furthermore, we studied the impact of different HMGB-1 isoforms on monocyte adhesion in vitro. Methods We included 77 DCM patients divided by median time point of death after first hospital admission into “early death”, “late death” and “alive” group. MD-2 was quantified by means of ELISA. MD-2 and HMGB1 was quantified by means of ELISA. Statistical analysis was performed using a linear regression model. Human umbilical vein endothelial cells (HUVEC; n=6) were treated for 48h with two isoforms of HMGB1 (disulfide (ds) and fully reduced (fr)) alone and in combination with MD-2. Subsequently, those activated HUVEC were incubated with fresh isolated peripheral blood mononuclear cells (PBMCs) for 20 min. Finally, monocyte adhesion was quantified using multicolour FACS. Results At baseline, we found significantly increased sMD-2 level in the “early death” group (591.3±75.5 ng/ml) compared to the “later death” group (369.2±46.5 ng/ml; p=0.015) and the “alive” group (303.2±18.1 ng/ml; p<0.001). Likewise, we could demonstrate significantly increased levels of HMGB1 in the “early death” group (0.93±0.14 ng/ml) compared to the “later death” (0.57±0.17 ng/ml; p=0.04) and the “alive” group (0.49±0.06 ng/ml; p<0.001). In all patients who died during the observation period, sMD-2 and HMGB1 plasma levels showed a positive correlation. In vitro, we could demonstrate a significantly increased monocyte adhesion on HUVECs in the dsHMGB1 and the frHMGB1 group compared to controls (p=0.001; p=0.004). In contrast, the dsHMGB1 MD-2 group showed a significantly decreased monocyte adhesion on HUVECs compared to dsHMGB1 treatment alone (p=0.049). In the frHMGB1 MD-2 group, however, the reduction of the monocyte adhesion was less pronounced and did not reach significance (Fig. 1). Conclusion Our findings give a first hint that the interplay between HMGB1 and MD-2 is particularly involved in the development and progression of DCM. Furthermore, the data suggest that soluble MD-2 is capable of reducing the pro-inflammatory effects of dsHMGB1 but not of frHMGB1


Cytotherapy ◽  
2017 ◽  
Vol 19 (8) ◽  
pp. 947-961 ◽  
Author(s):  
M. Dolores Carmona ◽  
Sagrario Cañadillas ◽  
Miguel Romero ◽  
Alfonso Blanco ◽  
Sonia Nogueras ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document