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 (...
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Wiley
2018-01-01
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Series: | Mediators of Inflammation |
Online Access: | http://dx.doi.org/10.1155/2018/8237209 |
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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. |
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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 |
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