A comparison of the effects of monotherapy with rosuvastatin, atorvastatin or ezetimibe versus combination treatment with rosuvastatin-ezetimibe and atorvastatin-ezetimibe on the integrity of vascular endothelial cells damaged by oxidized cholesterol.

Dyslipidemia, atherosclerosis, and cardiovascular events can be prevented, or treated, using statins, alone or in combination with ezetimibe. The aim of the study was to compare the direct pleiotropic effects of two commonly-used statins (atorvastatin, rosuvastatin), ezetimibe and their combinations...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Mateusz Niedzielski, Marlena Broncel, Paulina Gorzelak-Pabiś, Ewelina Woźniak
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2021
Materias:
R
Q
Acceso en línea:https://doaj.org/article/c175955ef4cd41948e3a340361c22c17
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:c175955ef4cd41948e3a340361c22c17
record_format dspace
spelling oai:doaj.org-article:c175955ef4cd41948e3a340361c22c172021-12-02T20:08:29ZA comparison of the effects of monotherapy with rosuvastatin, atorvastatin or ezetimibe versus combination treatment with rosuvastatin-ezetimibe and atorvastatin-ezetimibe on the integrity of vascular endothelial cells damaged by oxidized cholesterol.1932-620310.1371/journal.pone.0256996https://doaj.org/article/c175955ef4cd41948e3a340361c22c172021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256996https://doaj.org/toc/1932-6203Dyslipidemia, atherosclerosis, and cardiovascular events can be prevented, or treated, using statins, alone or in combination with ezetimibe. The aim of the study was to compare the direct pleiotropic effects of two commonly-used statins (atorvastatin, rosuvastatin), ezetimibe and their combinations on endothelial cells damaged by oxidized cholesterol. HUVEC cultures were stimulated for 20 hours with atorvastatin (5 μM; 2793 ng/mL), rosuvastatin (10 μM; 4815 ng/mL), ezetimibe (1.22 μM; 500 ng/mL), atorvastatin plus ezetimibe (5 μM + 1.22 μM; 2793 ng/mL + 500 ng/mL) and rosuvastatin plus ezetimibe (10 μM + 1.22 μM; 4815 ng/mL + 500ng/mL) in separate groups, with or without 25-hydroxycholesterol pre-incubation (24.83 μM; 10 μg/mL; four hours then washout). HUVEC integrity was measured in the RTCA-DP xCELLigence system. The mRNA expression and protein levels of ZO-1, OCLN, ICAM-1 were analyzed by real-time PCR and ELISA. Pre-incubation with 25-OHC resulted in decreased endothelial cell integrity (p<0.001), decreased expression of ZO-1 mRNA (p<0.05) and protein levels (p<0.05), OCLN mRNA (p<0.05) and protein levels (p<0.05) and increased ICAM-1 mRNA (p<0.001) and protein levels (p<0.001) compared to the control group. Incubation with rosuvastatin (12h p<0.01; 24h p<0.001) and atorvastatin (only 12h p<0.05) restored HUVEC integrity. Subsequent incubation with rosuvastatin increased ZO-1 mRNA (p<0.001) and protein (p<0.001) levels. Subsequent addition of ezetimibe increased ZO-1 mRNA level (p<0.001) but not protein level. Furthermore, only incubation with rosuvastatin increased OCLN mRNA (p<0.05) and protein (p<0.05) levels. In each drug-stimulated group, both ICAM-1 mRNA and protein levels were reduced after initial incubation with oxysterol (p<0.05). 25-hydroxycholesterol disrupts endothelial integrity, decreases the mRNA and protein levels of tight junction, and increases those of intercellular adhesion molecules. Both rosuvastatin and atorvastatin can improve endothelial integrity, but only rosuvastatin can completely abolish the effect of oxysterol. The combination of statins with ezetimibe has less direct effect on the endothelial barrier than the statins alone.Mateusz NiedzielskiMarlena BroncelPaulina Gorzelak-PabiśEwelina WoźniakPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0256996 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Mateusz Niedzielski
Marlena Broncel
Paulina Gorzelak-Pabiś
Ewelina Woźniak
A comparison of the effects of monotherapy with rosuvastatin, atorvastatin or ezetimibe versus combination treatment with rosuvastatin-ezetimibe and atorvastatin-ezetimibe on the integrity of vascular endothelial cells damaged by oxidized cholesterol.
description Dyslipidemia, atherosclerosis, and cardiovascular events can be prevented, or treated, using statins, alone or in combination with ezetimibe. The aim of the study was to compare the direct pleiotropic effects of two commonly-used statins (atorvastatin, rosuvastatin), ezetimibe and their combinations on endothelial cells damaged by oxidized cholesterol. HUVEC cultures were stimulated for 20 hours with atorvastatin (5 μM; 2793 ng/mL), rosuvastatin (10 μM; 4815 ng/mL), ezetimibe (1.22 μM; 500 ng/mL), atorvastatin plus ezetimibe (5 μM + 1.22 μM; 2793 ng/mL + 500 ng/mL) and rosuvastatin plus ezetimibe (10 μM + 1.22 μM; 4815 ng/mL + 500ng/mL) in separate groups, with or without 25-hydroxycholesterol pre-incubation (24.83 μM; 10 μg/mL; four hours then washout). HUVEC integrity was measured in the RTCA-DP xCELLigence system. The mRNA expression and protein levels of ZO-1, OCLN, ICAM-1 were analyzed by real-time PCR and ELISA. Pre-incubation with 25-OHC resulted in decreased endothelial cell integrity (p<0.001), decreased expression of ZO-1 mRNA (p<0.05) and protein levels (p<0.05), OCLN mRNA (p<0.05) and protein levels (p<0.05) and increased ICAM-1 mRNA (p<0.001) and protein levels (p<0.001) compared to the control group. Incubation with rosuvastatin (12h p<0.01; 24h p<0.001) and atorvastatin (only 12h p<0.05) restored HUVEC integrity. Subsequent incubation with rosuvastatin increased ZO-1 mRNA (p<0.001) and protein (p<0.001) levels. Subsequent addition of ezetimibe increased ZO-1 mRNA level (p<0.001) but not protein level. Furthermore, only incubation with rosuvastatin increased OCLN mRNA (p<0.05) and protein (p<0.05) levels. In each drug-stimulated group, both ICAM-1 mRNA and protein levels were reduced after initial incubation with oxysterol (p<0.05). 25-hydroxycholesterol disrupts endothelial integrity, decreases the mRNA and protein levels of tight junction, and increases those of intercellular adhesion molecules. Both rosuvastatin and atorvastatin can improve endothelial integrity, but only rosuvastatin can completely abolish the effect of oxysterol. The combination of statins with ezetimibe has less direct effect on the endothelial barrier than the statins alone.
format article
author Mateusz Niedzielski
Marlena Broncel
Paulina Gorzelak-Pabiś
Ewelina Woźniak
author_facet Mateusz Niedzielski
Marlena Broncel
Paulina Gorzelak-Pabiś
Ewelina Woźniak
author_sort Mateusz Niedzielski
title A comparison of the effects of monotherapy with rosuvastatin, atorvastatin or ezetimibe versus combination treatment with rosuvastatin-ezetimibe and atorvastatin-ezetimibe on the integrity of vascular endothelial cells damaged by oxidized cholesterol.
title_short A comparison of the effects of monotherapy with rosuvastatin, atorvastatin or ezetimibe versus combination treatment with rosuvastatin-ezetimibe and atorvastatin-ezetimibe on the integrity of vascular endothelial cells damaged by oxidized cholesterol.
title_full A comparison of the effects of monotherapy with rosuvastatin, atorvastatin or ezetimibe versus combination treatment with rosuvastatin-ezetimibe and atorvastatin-ezetimibe on the integrity of vascular endothelial cells damaged by oxidized cholesterol.
title_fullStr A comparison of the effects of monotherapy with rosuvastatin, atorvastatin or ezetimibe versus combination treatment with rosuvastatin-ezetimibe and atorvastatin-ezetimibe on the integrity of vascular endothelial cells damaged by oxidized cholesterol.
title_full_unstemmed A comparison of the effects of monotherapy with rosuvastatin, atorvastatin or ezetimibe versus combination treatment with rosuvastatin-ezetimibe and atorvastatin-ezetimibe on the integrity of vascular endothelial cells damaged by oxidized cholesterol.
title_sort comparison of the effects of monotherapy with rosuvastatin, atorvastatin or ezetimibe versus combination treatment with rosuvastatin-ezetimibe and atorvastatin-ezetimibe on the integrity of vascular endothelial cells damaged by oxidized cholesterol.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/c175955ef4cd41948e3a340361c22c17
work_keys_str_mv AT mateuszniedzielski acomparisonoftheeffectsofmonotherapywithrosuvastatinatorvastatinorezetimibeversuscombinationtreatmentwithrosuvastatinezetimibeandatorvastatinezetimibeontheintegrityofvascularendothelialcellsdamagedbyoxidizedcholesterol
AT marlenabroncel acomparisonoftheeffectsofmonotherapywithrosuvastatinatorvastatinorezetimibeversuscombinationtreatmentwithrosuvastatinezetimibeandatorvastatinezetimibeontheintegrityofvascularendothelialcellsdamagedbyoxidizedcholesterol
AT paulinagorzelakpabis acomparisonoftheeffectsofmonotherapywithrosuvastatinatorvastatinorezetimibeversuscombinationtreatmentwithrosuvastatinezetimibeandatorvastatinezetimibeontheintegrityofvascularendothelialcellsdamagedbyoxidizedcholesterol
AT ewelinawozniak acomparisonoftheeffectsofmonotherapywithrosuvastatinatorvastatinorezetimibeversuscombinationtreatmentwithrosuvastatinezetimibeandatorvastatinezetimibeontheintegrityofvascularendothelialcellsdamagedbyoxidizedcholesterol
AT mateuszniedzielski comparisonoftheeffectsofmonotherapywithrosuvastatinatorvastatinorezetimibeversuscombinationtreatmentwithrosuvastatinezetimibeandatorvastatinezetimibeontheintegrityofvascularendothelialcellsdamagedbyoxidizedcholesterol
AT marlenabroncel comparisonoftheeffectsofmonotherapywithrosuvastatinatorvastatinorezetimibeversuscombinationtreatmentwithrosuvastatinezetimibeandatorvastatinezetimibeontheintegrityofvascularendothelialcellsdamagedbyoxidizedcholesterol
AT paulinagorzelakpabis comparisonoftheeffectsofmonotherapywithrosuvastatinatorvastatinorezetimibeversuscombinationtreatmentwithrosuvastatinezetimibeandatorvastatinezetimibeontheintegrityofvascularendothelialcellsdamagedbyoxidizedcholesterol
AT ewelinawozniak comparisonoftheeffectsofmonotherapywithrosuvastatinatorvastatinorezetimibeversuscombinationtreatmentwithrosuvastatinezetimibeandatorvastatinezetimibeontheintegrityofvascularendothelialcellsdamagedbyoxidizedcholesterol
_version_ 1718375206277349376