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Activation of transforming growth factor-β(1 )and early atherosclerosis in systemic lupus erythematosus
The efficiency of activating latent transforming growth factor (TGF)-β(1 )in systemic lupus erythematosus (SLE) may control the balance between inflammation and fibrosis, modulating the disease phenotype. To test this hypothesis we studied the ability to activate TGF-β(1 )in SLE patients and control...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2006
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1526639/ https://www.ncbi.nlm.nih.gov/pubmed/16646981 http://dx.doi.org/10.1186/ar1951 |
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author | Jackson, Michelle Ahmad, Yasmeen Bruce, Ian N Coupes, Beatrice Brenchley, Paul EC |
author_facet | Jackson, Michelle Ahmad, Yasmeen Bruce, Ian N Coupes, Beatrice Brenchley, Paul EC |
author_sort | Jackson, Michelle |
collection | PubMed |
description | The efficiency of activating latent transforming growth factor (TGF)-β(1 )in systemic lupus erythematosus (SLE) may control the balance between inflammation and fibrosis, modulating the disease phenotype. To test this hypothesis we studied the ability to activate TGF-β(1 )in SLE patients and control individuals within the context of inflammatory disease activity, cumulative organ damage and early atherosclerosis. An Activation Index (AI) for TGF-β(1 )was determined for 32 patients with SLE and 33 age-matched and sex-matched control individuals by quantifying the increase in active TGF-β(1 )under controlled standard conditions. Apoptosis in peripheral blood mononuclear cells was determined by fluorescence-activated cell sorting. Carotid artery intima-media thickness was measured using standard Doppler ultrasound. These measures were compared between patients and control individuals. In an analysis conducted in patients, we assessed the associations of these measures with SLE phenotype, including early atherosclerosis. Both intima-media thickness and TGF-β(1 )AI for SLE patients were within the normal range. There was a significant inverse association between TGF-β(1 )AI and levels of apoptosis in peripheral blood mononuclear cells after 24 hours in culture for both SLE patients and control individuals. Only in SLE patients was there a significant negative correlation between TGF-β(1 )AI and low-density lipoprotein cholesterol (r = -0.404; P = 0.022) and between TGF-β(1 )AI and carotid artery intima-media thickness (r = -0.587; P = 0.0004). A low AI was associated with irreversible damage (SLICC [Systemic Lupus International Collaborating Clinics] Damage Index ≥1) and was inversely correlated with disease duration. Intima-media thickness was significantly linked to total cholesterol (r = 0.371; P = 0.037). To conclude, in SLE low normal TGF-β(1 )activation was linked with increased lymphocyte apoptosis, irreversible organ damage, disease duration, calculated low-density lipoprotein levels and increased carotid IMT, and may contribute to the development of early atherosclerosis. |
format | Text |
id | pubmed-1526639 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-15266392006-08-04 Activation of transforming growth factor-β(1 )and early atherosclerosis in systemic lupus erythematosus Jackson, Michelle Ahmad, Yasmeen Bruce, Ian N Coupes, Beatrice Brenchley, Paul EC Arthritis Res Ther Research Article The efficiency of activating latent transforming growth factor (TGF)-β(1 )in systemic lupus erythematosus (SLE) may control the balance between inflammation and fibrosis, modulating the disease phenotype. To test this hypothesis we studied the ability to activate TGF-β(1 )in SLE patients and control individuals within the context of inflammatory disease activity, cumulative organ damage and early atherosclerosis. An Activation Index (AI) for TGF-β(1 )was determined for 32 patients with SLE and 33 age-matched and sex-matched control individuals by quantifying the increase in active TGF-β(1 )under controlled standard conditions. Apoptosis in peripheral blood mononuclear cells was determined by fluorescence-activated cell sorting. Carotid artery intima-media thickness was measured using standard Doppler ultrasound. These measures were compared between patients and control individuals. In an analysis conducted in patients, we assessed the associations of these measures with SLE phenotype, including early atherosclerosis. Both intima-media thickness and TGF-β(1 )AI for SLE patients were within the normal range. There was a significant inverse association between TGF-β(1 )AI and levels of apoptosis in peripheral blood mononuclear cells after 24 hours in culture for both SLE patients and control individuals. Only in SLE patients was there a significant negative correlation between TGF-β(1 )AI and low-density lipoprotein cholesterol (r = -0.404; P = 0.022) and between TGF-β(1 )AI and carotid artery intima-media thickness (r = -0.587; P = 0.0004). A low AI was associated with irreversible damage (SLICC [Systemic Lupus International Collaborating Clinics] Damage Index ≥1) and was inversely correlated with disease duration. Intima-media thickness was significantly linked to total cholesterol (r = 0.371; P = 0.037). To conclude, in SLE low normal TGF-β(1 )activation was linked with increased lymphocyte apoptosis, irreversible organ damage, disease duration, calculated low-density lipoprotein levels and increased carotid IMT, and may contribute to the development of early atherosclerosis. BioMed Central 2006 2006-04-28 /pmc/articles/PMC1526639/ /pubmed/16646981 http://dx.doi.org/10.1186/ar1951 Text en Copyright © 2006 Jackson et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Jackson, Michelle Ahmad, Yasmeen Bruce, Ian N Coupes, Beatrice Brenchley, Paul EC Activation of transforming growth factor-β(1 )and early atherosclerosis in systemic lupus erythematosus |
title | Activation of transforming growth factor-β(1 )and early atherosclerosis in systemic lupus erythematosus |
title_full | Activation of transforming growth factor-β(1 )and early atherosclerosis in systemic lupus erythematosus |
title_fullStr | Activation of transforming growth factor-β(1 )and early atherosclerosis in systemic lupus erythematosus |
title_full_unstemmed | Activation of transforming growth factor-β(1 )and early atherosclerosis in systemic lupus erythematosus |
title_short | Activation of transforming growth factor-β(1 )and early atherosclerosis in systemic lupus erythematosus |
title_sort | activation of transforming growth factor-β(1 )and early atherosclerosis in systemic lupus erythematosus |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1526639/ https://www.ncbi.nlm.nih.gov/pubmed/16646981 http://dx.doi.org/10.1186/ar1951 |
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