Variability of MMP/TIMP and TGF-β1 Receptors throughout the Clinical Progression of Chronic Venous Disease
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/107694 https://doi.org/10.3390/ijms19010006 |
Resumo: | Chronic venous disease (CVeD) is a prevalent condition with a significant socioeconomic burden, yet the pathophysiology is only just beginning to be understood. Previous studies concerning the dysregulation of matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases (TIMPs)) within the varicose vein wall are inconsistent and disregard clinical progression. Moreover, it is highly plausible that MMP and TIMP expression/activity is affected by transforming growth factor (TGF)-β1 and its signaling receptors (TGFβRs) expression/activity in the vein wall. A case-control study was undertaken to analyze genetic and immunohistochemical differences between healthy (n = 13) and CVeD (early stages: n = 19; advanced stages: n = 12) great saphenous vein samples. Samples were grouped based on anatomic harvest site and subjected to quantitative polymerase chain reaction for MMP1, MMP2, MMP8, MMP9, MMP12, MMP13, TIMP1, TIMP2, TIMP3, TIMP4, TGFβR1, TGFβR2, and TGFβR3 gene expression analysis, and then to immunohistochemistry for immunolocalization of MMP2, TIMP2, and TGFβR2. Decreased gene expression of MMP12, TIMP2, TIMP3, TIMP4, and TGFβR2 was found in varicose veins when compared to controls. Regarding CVeD clinical progression, two facts arose: results across anatomical regions were uneven; decreased gene expression of MMP9 and TGFβR3 and increased gene expression of MMP2 and TIMP3 were found in advanced clinical stages. Most immunohistochemistry results for tunica intima were coherent with qPCR results. In conclusion, decreased expression of TGFβRs might suggest a reduction in TGF-β1 participation in the MMP/TIMP imbalance throughout CVeD progression. Further studies about molecular events in the varicose vein wall are required and should take into consideration the venous anatomical region and CVeD clinical progression. |
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Variability of MMP/TIMP and TGF-β1 Receptors throughout the Clinical Progression of Chronic Venous Diseasechronic venous diseasematrix metalloproteinases (MMPs)tissue inhibitors of metalloproteinases (TIMPs)Transforming growth factor (TGF)-βvaricose veingene expressionAdultAgedAged, 80 and overCase-Control StudiesChronic DiseaseCross-Sectional StudiesFemaleGene ExpressionHumansMaleMatrix MetalloproteinasesMiddle AgedReceptors, Transforming Growth Factor betaSaphenous VeinTissue Inhibitor of MetalloproteinasesTransforming Growth Factor beta1Tunica IntimaVaricose VeinsDisease ProgressionChronic venous disease (CVeD) is a prevalent condition with a significant socioeconomic burden, yet the pathophysiology is only just beginning to be understood. Previous studies concerning the dysregulation of matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases (TIMPs)) within the varicose vein wall are inconsistent and disregard clinical progression. Moreover, it is highly plausible that MMP and TIMP expression/activity is affected by transforming growth factor (TGF)-β1 and its signaling receptors (TGFβRs) expression/activity in the vein wall. A case-control study was undertaken to analyze genetic and immunohistochemical differences between healthy (n = 13) and CVeD (early stages: n = 19; advanced stages: n = 12) great saphenous vein samples. Samples were grouped based on anatomic harvest site and subjected to quantitative polymerase chain reaction for MMP1, MMP2, MMP8, MMP9, MMP12, MMP13, TIMP1, TIMP2, TIMP3, TIMP4, TGFβR1, TGFβR2, and TGFβR3 gene expression analysis, and then to immunohistochemistry for immunolocalization of MMP2, TIMP2, and TGFβR2. Decreased gene expression of MMP12, TIMP2, TIMP3, TIMP4, and TGFβR2 was found in varicose veins when compared to controls. Regarding CVeD clinical progression, two facts arose: results across anatomical regions were uneven; decreased gene expression of MMP9 and TGFβR3 and increased gene expression of MMP2 and TIMP3 were found in advanced clinical stages. Most immunohistochemistry results for tunica intima were coherent with qPCR results. In conclusion, decreased expression of TGFβRs might suggest a reduction in TGF-β1 participation in the MMP/TIMP imbalance throughout CVeD progression. Further studies about molecular events in the varicose vein wall are required and should take into consideration the venous anatomical region and CVeD clinical progression.MDPI2017-12-21info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/107694http://hdl.handle.net/10316/107694https://doi.org/10.3390/ijms19010006eng1422-0067Serralheiro, PedroNovais, AntónioCairrão, ElisaMaia, CláudioAlmeida, Carlos M. CostaVerde, Ignacioinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-27T10:28:02Zoai:estudogeral.uc.pt:10316/107694Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:24:01.003135Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Variability of MMP/TIMP and TGF-β1 Receptors throughout the Clinical Progression of Chronic Venous Disease |
title |
Variability of MMP/TIMP and TGF-β1 Receptors throughout the Clinical Progression of Chronic Venous Disease |
spellingShingle |
Variability of MMP/TIMP and TGF-β1 Receptors throughout the Clinical Progression of Chronic Venous Disease Serralheiro, Pedro chronic venous disease matrix metalloproteinases (MMPs) tissue inhibitors of metalloproteinases (TIMPs) Transforming growth factor (TGF)-β varicose vein gene expression Adult Aged Aged, 80 and over Case-Control Studies Chronic Disease Cross-Sectional Studies Female Gene Expression Humans Male Matrix Metalloproteinases Middle Aged Receptors, Transforming Growth Factor beta Saphenous Vein Tissue Inhibitor of Metalloproteinases Transforming Growth Factor beta1 Tunica Intima Varicose Veins Disease Progression |
title_short |
Variability of MMP/TIMP and TGF-β1 Receptors throughout the Clinical Progression of Chronic Venous Disease |
title_full |
Variability of MMP/TIMP and TGF-β1 Receptors throughout the Clinical Progression of Chronic Venous Disease |
title_fullStr |
Variability of MMP/TIMP and TGF-β1 Receptors throughout the Clinical Progression of Chronic Venous Disease |
title_full_unstemmed |
Variability of MMP/TIMP and TGF-β1 Receptors throughout the Clinical Progression of Chronic Venous Disease |
title_sort |
Variability of MMP/TIMP and TGF-β1 Receptors throughout the Clinical Progression of Chronic Venous Disease |
author |
Serralheiro, Pedro |
author_facet |
Serralheiro, Pedro Novais, António Cairrão, Elisa Maia, Cláudio Almeida, Carlos M. Costa Verde, Ignacio |
author_role |
author |
author2 |
Novais, António Cairrão, Elisa Maia, Cláudio Almeida, Carlos M. Costa Verde, Ignacio |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Serralheiro, Pedro Novais, António Cairrão, Elisa Maia, Cláudio Almeida, Carlos M. Costa Verde, Ignacio |
dc.subject.por.fl_str_mv |
chronic venous disease matrix metalloproteinases (MMPs) tissue inhibitors of metalloproteinases (TIMPs) Transforming growth factor (TGF)-β varicose vein gene expression Adult Aged Aged, 80 and over Case-Control Studies Chronic Disease Cross-Sectional Studies Female Gene Expression Humans Male Matrix Metalloproteinases Middle Aged Receptors, Transforming Growth Factor beta Saphenous Vein Tissue Inhibitor of Metalloproteinases Transforming Growth Factor beta1 Tunica Intima Varicose Veins Disease Progression |
topic |
chronic venous disease matrix metalloproteinases (MMPs) tissue inhibitors of metalloproteinases (TIMPs) Transforming growth factor (TGF)-β varicose vein gene expression Adult Aged Aged, 80 and over Case-Control Studies Chronic Disease Cross-Sectional Studies Female Gene Expression Humans Male Matrix Metalloproteinases Middle Aged Receptors, Transforming Growth Factor beta Saphenous Vein Tissue Inhibitor of Metalloproteinases Transforming Growth Factor beta1 Tunica Intima Varicose Veins Disease Progression |
description |
Chronic venous disease (CVeD) is a prevalent condition with a significant socioeconomic burden, yet the pathophysiology is only just beginning to be understood. Previous studies concerning the dysregulation of matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases (TIMPs)) within the varicose vein wall are inconsistent and disregard clinical progression. Moreover, it is highly plausible that MMP and TIMP expression/activity is affected by transforming growth factor (TGF)-β1 and its signaling receptors (TGFβRs) expression/activity in the vein wall. A case-control study was undertaken to analyze genetic and immunohistochemical differences between healthy (n = 13) and CVeD (early stages: n = 19; advanced stages: n = 12) great saphenous vein samples. Samples were grouped based on anatomic harvest site and subjected to quantitative polymerase chain reaction for MMP1, MMP2, MMP8, MMP9, MMP12, MMP13, TIMP1, TIMP2, TIMP3, TIMP4, TGFβR1, TGFβR2, and TGFβR3 gene expression analysis, and then to immunohistochemistry for immunolocalization of MMP2, TIMP2, and TGFβR2. Decreased gene expression of MMP12, TIMP2, TIMP3, TIMP4, and TGFβR2 was found in varicose veins when compared to controls. Regarding CVeD clinical progression, two facts arose: results across anatomical regions were uneven; decreased gene expression of MMP9 and TGFβR3 and increased gene expression of MMP2 and TIMP3 were found in advanced clinical stages. Most immunohistochemistry results for tunica intima were coherent with qPCR results. In conclusion, decreased expression of TGFβRs might suggest a reduction in TGF-β1 participation in the MMP/TIMP imbalance throughout CVeD progression. Further studies about molecular events in the varicose vein wall are required and should take into consideration the venous anatomical region and CVeD clinical progression. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-12-21 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/107694 http://hdl.handle.net/10316/107694 https://doi.org/10.3390/ijms19010006 |
url |
http://hdl.handle.net/10316/107694 https://doi.org/10.3390/ijms19010006 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1422-0067 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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