The cell-free DNA (cfDNA) is always present in plasma, and it is biomarker of growing interest in prenatal diagnostics as well as in oncology and transplantology for therapy efficiency monitoring. But does this cfDNA have a physiological role? Here we show that cfDNA presence and clearance in plasma of healthy individuals plays an indispensable role in immune system regulation. We exposed THP1 cells to healthy individuals' plasma with (NP) and without (TP) cfDNA. In cells treated with NP, we found elevated expression of genes whose products maintain immune system homeostasis. Exposure of cells to TP triggered an innate immune response (IIR), documented particularly by elevated expression of pro-inflammatory interleukin 8. The results of mass spectrometry showed a higher abundance of proteins associated with IIR activation due to the regulation of complement cascade in cells cultivated with TP. These expression profiles provide evidence that the presence of cfDNA and its clearance in plasma of healthy individuals regulate fundamental mechanisms of the inflammation process and tissue homeostasis. The detailed understanding how neutrophil extracellular traps and their naturally occurring degradation products affect the performance of immune system is of crucial interest for future medical applications.
- MeSH
- biologické markery krev MeSH
- chromatografie kapalinová MeSH
- dospělí MeSH
- extracelulární pasti imunologie MeSH
- hmotnostní spektrometrie MeSH
- krevní plazma MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- monocyty imunologie MeSH
- přirozená imunita * MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- tandemová hmotnostní spektrometrie MeSH
- THP-1 buňky MeSH
- volné cirkulující nukleové kyseliny krev MeSH
- zánět MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Since the late 1990s, a growing number of clinical studies have indicated that long-term permanent right ventricular (RV) apical pacing will induce severe complications such as development of heart failure, increased burden of atrial fibrillation leading to decreased quality of life. AIM OF THE STUDY: To investigate whether cardiac resynchronization therapy (CRT) using biventricular (BiV) pacing can prevent the development of left ventricular (LV) dysfunction, LV remodelling, worsening of the clinical status and quality of life in chronically RV paced patients with normal LV ejection fraction (EF). METHODS AND RESULTS: A total of 127 patients with Class I indication for permanent cardiac pacing and without established indication for CRT were subjected to 6 months of RV and BiV pacing in a patient-blinded, randomized crossover trial. Treatment effects of BiV pacing were evaluated for LV function, LV remodelling and clinical status. As compared with RV pacing, BiV pacing did not significantly prevent the decrease of LV function [LVEF 61.0 % (36.0; 68.0) vs 60.5 % (38.5; 67.5) in RV pacing], did not change the functional class according to the New York Heart Association [52 % in Class II vs 53.9 % in Class II in RV pacing, and 3.9 % in Class III vs 6.9 % in Class III in RV pacing], and did not present any changes in quality of life [32.5 (18.0; 80.0) vs 32.0 (21.0; 47.0) indexes in RV pacing]. CONCLUSION: BiV pacing, compared to RV pacing, did not change LV function and quality of life in patients with the absence of LV dysfunction or remodelling, standard bradycardia pacing indications in a pilot phase (12- month follow-up) of the TUGENDHAT trial. The final report will be published after 60-month follow-up termination (Tab. 5, Fig. 3, Ref. 30).
- MeSH
- bradykardie terapie MeSH
- časové faktory MeSH
- fibrilace síní prevence a kontrola MeSH
- jednoduchá slepá metoda MeSH
- klinické křížové studie MeSH
- kvalita života * MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- pilotní projekty MeSH
- prospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- srdeční resynchronizační terapie metody MeSH
- srdeční selhání prevence a kontrola MeSH
- systola MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- Publikační typ
- abstrakt z konference MeSH
