Role of Mannose-Binding Lectin and Complement Activation in Venous Thromboembolism
The complement and coagulation systems are two interrelated plasma protein cascades. Evidence from observational and animal studies has proposed a role for the complement system in the development of venous thromboembolism (VTE), but the exact mechanisms remain obscure. The aim of this thesis was to...
Published in: | Journal of Thrombosis and Haemostasis |
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Language: | English |
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UiT The Arctic University of Norway
2019
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Online Access: | https://hdl.handle.net/10037/17027 |
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ftunivtroemsoe:oai:munin.uit.no:10037/17027 2023-05-15T18:34:57+02:00 Role of Mannose-Binding Lectin and Complement Activation in Venous Thromboembolism Liang, Robin Amanda 2019-12-17 https://hdl.handle.net/10037/17027 eng eng UiT The Arctic University of Norway UiT Norges arktiske universitet Paper I: Høiland, I.I., Liang, R.A., Brækkan, S.K., Pettersen, K., Ludviksen, J.K., Latysheva, N., … Hansen, J.B. (2019). Complement Activation Assessed by the Plasma Terminal Complement Complex and Future Risk of Venous Thromboembolism. Journal of Thrombosis and Haemostasis, 17 (6), 934-943. Also available at https://doi.org/10.1111/jth.14438 . Paper II: Liang, R.A., Høiland, I.I., Ueland, T., Aukrust, P., Snir, O., Hindberg, K., … Hansen, J.B. (2019). Plasma levels of Mannose-Binding Lectin and Future Risk of Venous Thromboembolism. Journal of Thrombosis and Haemostasis, 17 (10), 1661-1669. Also available in Munin at https://hdl.handle.net/10037/16191 . Paper III: Liang, R.A., Hindberg, K., Ueland, T., Aukrust, P., Snir, O., Brækkan, S.K., … Hansen, J.B. ABO Status Affects Plasma Mannose-Binding Lectin Levels and the Association Between MBL Levels and Risk of Venous Thromboembolism. (Manuscript). Available in the file “thesis_entire.pdf”. The Tromsø Study (Tromsø 4) data sets available upon request https://hdl.handle.net/10037/17027 embargoedAccess Copyright 2019 The Author(s) VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Hematology: 775 VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Hematologi: 775 DOKTOR-003 Doctoral thesis Doktorgradsavhandling 2019 ftunivtroemsoe https://doi.org/10.1111/jth.14438 2021-06-25T17:57:04Z The complement and coagulation systems are two interrelated plasma protein cascades. Evidence from observational and animal studies has proposed a role for the complement system in the development of venous thromboembolism (VTE), but the exact mechanisms remain obscure. The aim of this thesis was to investigate whether activation of the complement system impacts the risk of VTE and to investigate which pathways may be involved. The procoagulant properties of the lectin pathway, in particular, demanded closer inspection. Genetic variations associated with plasma levels of complement protein or activation products were also explored to discover novel genetic regulators that could potentially contribute to thrombosis risk. The fourth survey of the Tromsø Study was used as the parent cohort for all of the nested case-control studies discussed in this thesis. There were 462 individuals who experienced a VTE in the follow-up period (1994/95-2007). For each VTE case, two age- and sex-matched controls who were alive at the index date of the VTE event were randomly sampled from the source cohort. The findings in this thesis support a role for the complement system in the development of VTE. Higher baseline levels of complement activation as measured by the soluble terminal C5b-9 complement complex (TCC) were associated with future risk of VTE, as were high levels of plasma mannose-binding lectin (MBL). The rs8176719 SNP of the ABO gene, which determines O and non-O blood types and is itself a known risk factor for VTE, was found to be significantly associated with high plasma MBL levels. Individuals with high plasma MBL levels and type O blood were found to have a similar risk for VTE as individuals with non-O blood type, regardless of plasma MBL levels. These studies implicate that the lectin pathway is involved in the mechanisms leading to venous thrombosis. Functional studies are warranted. Additionally, the discovery of a relationship between blood type and plasma MBL levels requires further investigation, both alone and as a risk factor for venous thromboembolism. Doctoral or Postdoctoral Thesis Tromsø University of Tromsø: Munin Open Research Archive Tromsø Journal of Thrombosis and Haemostasis 17 6 934 943 |
institution |
Open Polar |
collection |
University of Tromsø: Munin Open Research Archive |
op_collection_id |
ftunivtroemsoe |
language |
English |
topic |
VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Hematology: 775 VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Hematologi: 775 DOKTOR-003 |
spellingShingle |
VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Hematology: 775 VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Hematologi: 775 DOKTOR-003 Liang, Robin Amanda Role of Mannose-Binding Lectin and Complement Activation in Venous Thromboembolism |
topic_facet |
VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Hematology: 775 VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Hematologi: 775 DOKTOR-003 |
description |
The complement and coagulation systems are two interrelated plasma protein cascades. Evidence from observational and animal studies has proposed a role for the complement system in the development of venous thromboembolism (VTE), but the exact mechanisms remain obscure. The aim of this thesis was to investigate whether activation of the complement system impacts the risk of VTE and to investigate which pathways may be involved. The procoagulant properties of the lectin pathway, in particular, demanded closer inspection. Genetic variations associated with plasma levels of complement protein or activation products were also explored to discover novel genetic regulators that could potentially contribute to thrombosis risk. The fourth survey of the Tromsø Study was used as the parent cohort for all of the nested case-control studies discussed in this thesis. There were 462 individuals who experienced a VTE in the follow-up period (1994/95-2007). For each VTE case, two age- and sex-matched controls who were alive at the index date of the VTE event were randomly sampled from the source cohort. The findings in this thesis support a role for the complement system in the development of VTE. Higher baseline levels of complement activation as measured by the soluble terminal C5b-9 complement complex (TCC) were associated with future risk of VTE, as were high levels of plasma mannose-binding lectin (MBL). The rs8176719 SNP of the ABO gene, which determines O and non-O blood types and is itself a known risk factor for VTE, was found to be significantly associated with high plasma MBL levels. Individuals with high plasma MBL levels and type O blood were found to have a similar risk for VTE as individuals with non-O blood type, regardless of plasma MBL levels. These studies implicate that the lectin pathway is involved in the mechanisms leading to venous thrombosis. Functional studies are warranted. Additionally, the discovery of a relationship between blood type and plasma MBL levels requires further investigation, both alone and as a risk factor for venous thromboembolism. |
format |
Doctoral or Postdoctoral Thesis |
author |
Liang, Robin Amanda |
author_facet |
Liang, Robin Amanda |
author_sort |
Liang, Robin Amanda |
title |
Role of Mannose-Binding Lectin and Complement Activation in Venous Thromboembolism |
title_short |
Role of Mannose-Binding Lectin and Complement Activation in Venous Thromboembolism |
title_full |
Role of Mannose-Binding Lectin and Complement Activation in Venous Thromboembolism |
title_fullStr |
Role of Mannose-Binding Lectin and Complement Activation in Venous Thromboembolism |
title_full_unstemmed |
Role of Mannose-Binding Lectin and Complement Activation in Venous Thromboembolism |
title_sort |
role of mannose-binding lectin and complement activation in venous thromboembolism |
publisher |
UiT The Arctic University of Norway |
publishDate |
2019 |
url |
https://hdl.handle.net/10037/17027 |
geographic |
Tromsø |
geographic_facet |
Tromsø |
genre |
Tromsø |
genre_facet |
Tromsø |
op_relation |
Paper I: Høiland, I.I., Liang, R.A., Brækkan, S.K., Pettersen, K., Ludviksen, J.K., Latysheva, N., … Hansen, J.B. (2019). Complement Activation Assessed by the Plasma Terminal Complement Complex and Future Risk of Venous Thromboembolism. Journal of Thrombosis and Haemostasis, 17 (6), 934-943. Also available at https://doi.org/10.1111/jth.14438 . Paper II: Liang, R.A., Høiland, I.I., Ueland, T., Aukrust, P., Snir, O., Hindberg, K., … Hansen, J.B. (2019). Plasma levels of Mannose-Binding Lectin and Future Risk of Venous Thromboembolism. Journal of Thrombosis and Haemostasis, 17 (10), 1661-1669. Also available in Munin at https://hdl.handle.net/10037/16191 . Paper III: Liang, R.A., Hindberg, K., Ueland, T., Aukrust, P., Snir, O., Brækkan, S.K., … Hansen, J.B. ABO Status Affects Plasma Mannose-Binding Lectin Levels and the Association Between MBL Levels and Risk of Venous Thromboembolism. (Manuscript). Available in the file “thesis_entire.pdf”. The Tromsø Study (Tromsø 4) data sets available upon request https://hdl.handle.net/10037/17027 |
op_rights |
embargoedAccess Copyright 2019 The Author(s) |
op_doi |
https://doi.org/10.1111/jth.14438 |
container_title |
Journal of Thrombosis and Haemostasis |
container_volume |
17 |
container_issue |
6 |
container_start_page |
934 |
op_container_end_page |
943 |
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1766219981013385216 |