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001-es BibID:BIBFORM074180
035-os BibID:(cikkazonosító)e0197890 (WOS)000434786600008 (Scopus)85048322440
Első szerző:Fejes Zsolt (molekuláris biológus)
Cím:Endothelial cell activation is attenuated by everolimus via transcriptional and post-transcriptional regulatory mechanisms after drug-eluting coronary stenting / Fejes Z., Czimmerer Z., Szük T., Póliska S., Horváth A., Balogh E., Jeney V., Váradi J., Fenyvesi F., Balla G., Édes I., Balla J., Kappelmayer J., Nagy B. Jr.
Dátum:2018
ISSN:1932-6203
Megjegyzések:We previously found higher level of endothelial cell (EC) activation in patients who suffered from in-stent restenosis after bare-metal stenting compared to subjects who underwent drug-eluting stenting (DES) showing no complications. Here we investigated the potential transcriptional and post-transcriptional regulatory mechanisms by which everolimus attenuated EC activation after DES. We studied the effect of everolimus on E-selectin (SELE) and VCAM1 mRNA levels when human coronary artery (HCAECs) and human umbilical vein ECs were challenged with recombinant TNF-? (100 ng/mL) for 1-24 hours in the presence or absence of everolimus using 0.5 ?M concentration locally maintained by DES. EC activation was evaluated via the levels of IL-1? and IL-6 mRNAs with miR-155 expression by RT-qPCR as well as the nuclear translocation of nuclear factor kappa beta (NF-?B) detected by fluorescence microscopy. To investigate the transcriptional regulation of E-selectin and VCAM-1, TNF-?-induced enhancer RNA (eRNA) expression at p65-bound enhancers in the neighboring genomic regions of SELE and VCAM1 genes, including SELE_-11Kb and VCAM1_-10Kb, were measured in HCAECs. Mature and precursor levels of E-selectin and VCAM-1 repressor miR-181b were quantified to analyze the post-transcriptional regulation of these genes in HCAECs. Circulating miR-181b was analyzed in plasma samples of stented subjects by stem-loop RT-qPCR. TNF-? highly elevated E-selectin and VCAM-1 expression at transcriptional level in ECs. Levels of mature, pre- and pri-miR-181b were repressed in ECs by TNF-?, while everolimus acted as a negative regulator of EC activation via inhibited translocation of NF-?B p65 subunit into cell nuclei, lowered eRNA expression at SELE and VCAM1 genes-associated enhancers and modulated expression of their post-transcriptional repressor miR-181b. Significant negative correlation was observed between plasma miR-181b and soluble E-selectin and VCAM-1 in patients. In conclusion, everolimus attenuates EC activation via reduced NF-?B p65 translocation causing decreased E-selectin and VCAM-1 expression at transcriptional and post-transcriptional level after DES.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
coronary stenting
endothelial cell
enhancer RNA
everolimus
inflammation
microRNA
Megjelenés:Plos One. - 13 : 6 (2018), p. 1-20. -
További szerzők:Czimmerer Zsolt (1981-) (molekuláris biológus) Szűk Tibor (1967-) (kardiológus) Póliska Szilárd (1978-) (biológus) Horváth Attila (1988-) (programtervező informatikus) Balogh Enikő (1987-) (molekuláris biológus) Jeney Viktória (1971-) (vegyész, kémia tanár) Váradi Judit (1973-) (gyógyszerész, gyógyszertechnológus) Fenyvesi Ferenc (1977-) (gyógyszerész, gyógyszertechnológus) Balla György (1953-) (csecsemő és gyermekgyógyász, neonatológus) Édes István (1952-) (kardiológus) Balla József (1959-) (belgyógyász, nephrológus) Kappelmayer János (1960-) (laboratóriumi szakorvos) Nagy Béla Jr. (1980-) (labordiagnosztikai szakorvos)
Pályázati támogatás:GINOP-2.3.2-15-2016-00043
GINOP
Internet cím:DOI
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001-es BibID:BIBFORM054156
Első szerző:Szűk Tibor (kardiológus)
Cím:Effects of ad hoc clopidogrel loading versus pre-treatment on P-selectin expression after coronary stent implantation / Tibor Szuk, Béla Nagy, Zsuzsanna Bereczky, Zsolt Koszegi, István Edes, János Kappelmayer
Dátum:2006
ISSN:0953-7104
Megjegyzések:Stents represent a thrombogenic surface where one of the earliest events is the deposition of platelets. Activated platelets express neoepitopes that enable them to form homo- and heterotypic aggregates and activate the coagulation system. In this study, we investigated the effects of ad hoc clopidogrel treatment compared to a clopidogrel pretreated group on platelet P-selectin expression. We found that after stent implantation in the ad hoc treated group, P-selectin expression decreased after 1 h, while the initial decrease in platelet count normalized after 4 h. Aspirin non-responsiveness did not influence the results. These data point to the beneficial effect of clopidogrel treatment in reducing platelet reactivity during stenting.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Drug Delivery Systems
Flow Cytometry
Humans
P-Selectin
Platelet Activation
Platelet Aggregation Inhibitors
Stents
Ticlopidine
Megjelenés:Platelets. - 17 : 5 (2006), p. 344-346. -
További szerzők:Nagy Béla Jr. (1980-) (labordiagnosztikai szakorvos) Bereczky Zsuzsanna (1974-) (orvosi laboratóriumi diagnosztika szakorvos) Kőszegi Zsolt (1962-) (kardiológus, belgyógyász) Édes István (1952-) (kardiológus) Kappelmayer János (1960-) (laboratóriumi szakorvos)
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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