Neutrophil Extracellular Traps and Thrombolysis Resistance: New Insights for Targeting Therapies
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064173%3A_____%2F24%3A43926838" target="_blank" >RIV/00064173:_____/24:43926838 - isvavai.cz</a>
Alternative codes found
RIV/61383082:_____/24:00001433 RIV/00216208:11110/24:10478567 RIV/00216208:11120/24:43926838
Result on the web
<a href="https://doi.org/10.1161/STROKEAHA.123.045225" target="_blank" >https://doi.org/10.1161/STROKEAHA.123.045225</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1161/STROKEAHA.123.045225" target="_blank" >10.1161/STROKEAHA.123.045225</a>
Alternative languages
Result language
angličtina
Original language name
Neutrophil Extracellular Traps and Thrombolysis Resistance: New Insights for Targeting Therapies
Original language description
BACKGROUND: Thrombosis is linked to neutrophil release of neutrophil extracellular traps (NETs). NETs are proposed as a mechanism of resistance to thrombolysis. This study intends to analyze the composition of thrombi retrieved after mechanical thrombectomy, estimate the age and organization of thrombi, and evaluate associations with the use of thrombolysis, antiplatelets, and heparin. METHODS: This retrospective observational study involved 72 samples (44 from cerebral and 28 coronary arteries), which were stained with hematoxylin and eosin, anti-NE (neutrophil elastase) antibody, and anti-histone H2B (histone H2B) antibody, representing different components in NET formation, all detectable during the later stages of NETosis, for histochemical and digital quantification of NET content. The histological and morphological evaluations of the specimens were correlated, through univariate and mediation analyses, with clinical information and therapy administered before intervention. RESULTS: The results demonstrated that the composition of cerebral and coronary thrombi differs, and there were significantly more lytic cerebral thrombi than coronary thrombi (66% versus 14%; P=0.005). There was a considerably higher expression of NETs in the cerebral thrombi as testified by the higher expression of H2B (P=0.031). Thrombolysis was remarkably associated with higher NE positivity (average marginal effect, 6.461 [95% CI, 0.7901-12.13]; P=0.02555), regardless of the origin of thrombi. There was no notable association between the administration of antiaggregant therapy/heparin and H2B/NE amount when adjusted for the thrombus location. Importantly, the age of the thrombus was the only independent predictor of NET content without any mediation of the thrombolytic treatment (P=0.014). CONCLUSIONS: The age of the thrombus is the driving force for NET content, which correlates with impaired clinical outcomes. The therapy that is currently administered does not modify NET content. This study supports the need to investigate new pharmacological approaches added to thrombolysis to prevent NET formation or enhance their disruption, such as recombinant human DNase I (deoxyribonuclease I).
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30201 - Cardiac and Cardiovascular systems
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Stroke
ISSN
0039-2499
e-ISSN
1524-4628
Volume of the periodical
55
Issue of the periodical within the volume
4
Country of publishing house
US - UNITED STATES
Number of pages
9
Pages from-to
963-971
UT code for WoS article
001236244100030
EID of the result in the Scopus database
2-s2.0-85188842018