Variability of MMP/TIMP and TGF-β1 Receptors throughout the Clinical Progression of Chronic Venous Disease

Detalhes bibliográficos
Autor(a) principal: Serralheiro, Pedro
Data de Publicação: 2017
Outros Autores: Novais, António, Cairrão, Elisa, Maia, Cláudio, Almeida, Carlos M. Costa, Verde, Ignacio
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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spelling 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
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dc.publisher.none.fl_str_mv MDPI
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