Analysis of Drug Effects on Primary Human Coronary Artery Endothelial Cells Activated by Serum Amyloid A

Background. RA patients have a higher incidence of cardiovascular diseases compared to the general population. Serum amyloid A (SAA) is an acute-phase protein, upregulated in sera of RA patients. Aim. To determine the effects of medications on SAA-stimulated human coronary artery endothelial cells (...

Full description

Saved in:
Bibliographic Details
Main Authors: K. Lakota, D. Hrušovar, M. Ogrič, K. Mrak-Poljšak, S. Čučnik, M. Tomšič, B. Božič, P. Žigon, S. Sodin-Semrl
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2018/8237209
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832545747131695104
author K. Lakota
D. Hrušovar
M. Ogrič
K. Mrak-Poljšak
S. Čučnik
M. Tomšič
B. Božič
P. Žigon
S. Sodin-Semrl
author_facet K. Lakota
D. Hrušovar
M. Ogrič
K. Mrak-Poljšak
S. Čučnik
M. Tomšič
B. Božič
P. Žigon
S. Sodin-Semrl
author_sort K. Lakota
collection DOAJ
description Background. RA patients have a higher incidence of cardiovascular diseases compared to the general population. Serum amyloid A (SAA) is an acute-phase protein, upregulated in sera of RA patients. Aim. To determine the effects of medications on SAA-stimulated human coronary artery endothelial cells (HCAEC). Methods. HCAEC were preincubated for 2 h with medications from sterile ampules (dexamethasone, methotrexate, certolizumab pegol, and etanercept), dissolved in medium (captopril) or DMSO (etoricoxib, rosiglitazone, meloxicam, fluvastatin, and diclofenac). Human recombinant apo-SAA was used to stimulate HCAEC at a final 1000 nM concentration for 24 hours. IL-6, IL-8, sVCAM-1, and PAI-1 were measured by ELISA. The number of viable cells was determined colorimetrically. Results. SAA-stimulated levels of released IL-6, IL-8, and sVCAM-1 from HCAEC were significantly attenuated by methotrexate, fluvastatin, and etoricoxib. Both certolizumab pegol and etanercept significantly decreased PAI-1 by an average of 43%. Rosiglitazone significantly inhibited sVCAM-1 by 58%. Conclusion. We observed marked influence of fluvastatin on lowering cytokine production in SAA-activated HCAEC. Methotrexate showed strong beneficial effects for lowering released Il-6, IL-8, and sVCAM-1. Interesting duality was observed for NSAIDs, with meloxicam exhibiting opposite-trend effects from diclofenac and etoricoxib. This represents unique insight into specific responsiveness of inflammatory-driven HCAEC relevant to atherosclerosis.
format Article
id doaj-art-e0644ff16a444fd89fe5b9e53e0f46f8
institution Kabale University
issn 0962-9351
1466-1861
language English
publishDate 2018-01-01
publisher Wiley
record_format Article
series Mediators of Inflammation
spelling doaj-art-e0644ff16a444fd89fe5b9e53e0f46f82025-02-03T07:24:58ZengWileyMediators of Inflammation0962-93511466-18612018-01-01201810.1155/2018/82372098237209Analysis of Drug Effects on Primary Human Coronary Artery Endothelial Cells Activated by Serum Amyloid AK. Lakota0D. Hrušovar1M. Ogrič2K. Mrak-Poljšak3S. Čučnik4M. Tomšič5B. Božič6P. Žigon7S. Sodin-Semrl8Department of Rheumatology, University Medical Centre Ljubljana, SI-1000 Ljubljana, SloveniaBlood Transfusion Center of Slovenia, Tissue Typing Centre, SI-1000 Ljubljana, SloveniaDepartment of Rheumatology, University Medical Centre Ljubljana, SI-1000 Ljubljana, SloveniaDepartment of Rheumatology, University Medical Centre Ljubljana, SI-1000 Ljubljana, SloveniaDepartment of Rheumatology, University Medical Centre Ljubljana, SI-1000 Ljubljana, SloveniaDepartment of Rheumatology, University Medical Centre Ljubljana, SI-1000 Ljubljana, SloveniaDepartment of Rheumatology, University Medical Centre Ljubljana, SI-1000 Ljubljana, SloveniaDepartment of Rheumatology, University Medical Centre Ljubljana, SI-1000 Ljubljana, SloveniaDepartment of Rheumatology, University Medical Centre Ljubljana, SI-1000 Ljubljana, SloveniaBackground. RA patients have a higher incidence of cardiovascular diseases compared to the general population. Serum amyloid A (SAA) is an acute-phase protein, upregulated in sera of RA patients. Aim. To determine the effects of medications on SAA-stimulated human coronary artery endothelial cells (HCAEC). Methods. HCAEC were preincubated for 2 h with medications from sterile ampules (dexamethasone, methotrexate, certolizumab pegol, and etanercept), dissolved in medium (captopril) or DMSO (etoricoxib, rosiglitazone, meloxicam, fluvastatin, and diclofenac). Human recombinant apo-SAA was used to stimulate HCAEC at a final 1000 nM concentration for 24 hours. IL-6, IL-8, sVCAM-1, and PAI-1 were measured by ELISA. The number of viable cells was determined colorimetrically. Results. SAA-stimulated levels of released IL-6, IL-8, and sVCAM-1 from HCAEC were significantly attenuated by methotrexate, fluvastatin, and etoricoxib. Both certolizumab pegol and etanercept significantly decreased PAI-1 by an average of 43%. Rosiglitazone significantly inhibited sVCAM-1 by 58%. Conclusion. We observed marked influence of fluvastatin on lowering cytokine production in SAA-activated HCAEC. Methotrexate showed strong beneficial effects for lowering released Il-6, IL-8, and sVCAM-1. Interesting duality was observed for NSAIDs, with meloxicam exhibiting opposite-trend effects from diclofenac and etoricoxib. This represents unique insight into specific responsiveness of inflammatory-driven HCAEC relevant to atherosclerosis.http://dx.doi.org/10.1155/2018/8237209
spellingShingle K. Lakota
D. Hrušovar
M. Ogrič
K. Mrak-Poljšak
S. Čučnik
M. Tomšič
B. Božič
P. Žigon
S. Sodin-Semrl
Analysis of Drug Effects on Primary Human Coronary Artery Endothelial Cells Activated by Serum Amyloid A
Mediators of Inflammation
title Analysis of Drug Effects on Primary Human Coronary Artery Endothelial Cells Activated by Serum Amyloid A
title_full Analysis of Drug Effects on Primary Human Coronary Artery Endothelial Cells Activated by Serum Amyloid A
title_fullStr Analysis of Drug Effects on Primary Human Coronary Artery Endothelial Cells Activated by Serum Amyloid A
title_full_unstemmed Analysis of Drug Effects on Primary Human Coronary Artery Endothelial Cells Activated by Serum Amyloid A
title_short Analysis of Drug Effects on Primary Human Coronary Artery Endothelial Cells Activated by Serum Amyloid A
title_sort analysis of drug effects on primary human coronary artery endothelial cells activated by serum amyloid a
url http://dx.doi.org/10.1155/2018/8237209
work_keys_str_mv AT klakota analysisofdrugeffectsonprimaryhumancoronaryarteryendothelialcellsactivatedbyserumamyloida
AT dhrusovar analysisofdrugeffectsonprimaryhumancoronaryarteryendothelialcellsactivatedbyserumamyloida
AT mogric analysisofdrugeffectsonprimaryhumancoronaryarteryendothelialcellsactivatedbyserumamyloida
AT kmrakpoljsak analysisofdrugeffectsonprimaryhumancoronaryarteryendothelialcellsactivatedbyserumamyloida
AT scucnik analysisofdrugeffectsonprimaryhumancoronaryarteryendothelialcellsactivatedbyserumamyloida
AT mtomsic analysisofdrugeffectsonprimaryhumancoronaryarteryendothelialcellsactivatedbyserumamyloida
AT bbozic analysisofdrugeffectsonprimaryhumancoronaryarteryendothelialcellsactivatedbyserumamyloida
AT pzigon analysisofdrugeffectsonprimaryhumancoronaryarteryendothelialcellsactivatedbyserumamyloida
AT ssodinsemrl analysisofdrugeffectsonprimaryhumancoronaryarteryendothelialcellsactivatedbyserumamyloida