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Circulating matrix metalloproteinases are associated with arterial stiffness in patients with type 1 diabetes: pooled analysis of three cohort studies

BACKGROUND: Altered regulation of extracellular matrix (ECM) composition by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) may contribute to arterial stiffening. We investigated associations between circulating MMP-1, -2, -3, -9, -10 and TIMP-1, and carotid-femor...

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Autores principales: Peeters, Stijn A., Engelen, Lian, Buijs, Jacqueline, Chaturvedi, Nish, Fuller, John H., Jorsal, Anders, Parving, Hans-Henrik, Tarnow, Lise, Theilade, Simone, Rossing, Peter, Schalkwijk, Casper G., Stehouwer, Coen D. A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5657128/
https://www.ncbi.nlm.nih.gov/pubmed/29070037
http://dx.doi.org/10.1186/s12933-017-0620-9
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author Peeters, Stijn A.
Engelen, Lian
Buijs, Jacqueline
Chaturvedi, Nish
Fuller, John H.
Jorsal, Anders
Parving, Hans-Henrik
Tarnow, Lise
Theilade, Simone
Rossing, Peter
Schalkwijk, Casper G.
Stehouwer, Coen D. A.
author_facet Peeters, Stijn A.
Engelen, Lian
Buijs, Jacqueline
Chaturvedi, Nish
Fuller, John H.
Jorsal, Anders
Parving, Hans-Henrik
Tarnow, Lise
Theilade, Simone
Rossing, Peter
Schalkwijk, Casper G.
Stehouwer, Coen D. A.
author_sort Peeters, Stijn A.
collection PubMed
description BACKGROUND: Altered regulation of extracellular matrix (ECM) composition by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) may contribute to arterial stiffening. We investigated associations between circulating MMP-1, -2, -3, -9, -10 and TIMP-1, and carotid-femoral pulse wave velocity (cfPWV) and pulse pressure (PP), as markers of arterial stiffness in type 1 diabetic patients. METHODS: Individuals with type 1 diabetes from three different cohorts were included in this study: EURODIAB Prospective Complications study (n = 509), LEACE (n = 370) and PROFIL (n = 638). Linear regression analyses were used to investigate cross-sectional associations between circulating levels of MMP-1, -2, -3, -9, -10, and TIMP-1 and cfPWV (n = 614) as well as office PP (n = 1517). Data on 24-h brachial and 24-h central PP were available in 638 individuals from PROFIL. Analyses were adjusted for age, sex, duration of diabetes, HbA1c, mean arterial pressure (MAP), and eGFR, and additionally for other cardiovascular risk factors and presence of vascular complications. RESULTS: After adjustment for potential confounders and presence of vascular complications, circulating MMP-3 was associated with cfPWV [β per 1 SD higher lnMMP3 0.29 m/s (0.02; 0.55)]. In addition, brachial and central 24-h PP measurements in PROFIL were significantly associated with MMP-2 [(1.40 (0.47:2.33) and 1.43 (0.63:2.23)]. Pooled data analysis showed significant associations of circulating levels of MMP-1 and MMP-2 with office PP [β per 1 SD higher lnMMP-1 and lnMMP-2 = − 0.83 mmHg (95% CI − 1.50; − 0.16) and = 1.33 mmHg (0.55; 2.10), respectively]. CONCLUSIONS: MMPs-1, -2, and -3 are independently associated with markers of arterial stiffening in patients with type 1 diabetes and may become therapeutic targets. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-017-0620-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-56571282017-10-31 Circulating matrix metalloproteinases are associated with arterial stiffness in patients with type 1 diabetes: pooled analysis of three cohort studies Peeters, Stijn A. Engelen, Lian Buijs, Jacqueline Chaturvedi, Nish Fuller, John H. Jorsal, Anders Parving, Hans-Henrik Tarnow, Lise Theilade, Simone Rossing, Peter Schalkwijk, Casper G. Stehouwer, Coen D. A. Cardiovasc Diabetol Original Investigation BACKGROUND: Altered regulation of extracellular matrix (ECM) composition by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) may contribute to arterial stiffening. We investigated associations between circulating MMP-1, -2, -3, -9, -10 and TIMP-1, and carotid-femoral pulse wave velocity (cfPWV) and pulse pressure (PP), as markers of arterial stiffness in type 1 diabetic patients. METHODS: Individuals with type 1 diabetes from three different cohorts were included in this study: EURODIAB Prospective Complications study (n = 509), LEACE (n = 370) and PROFIL (n = 638). Linear regression analyses were used to investigate cross-sectional associations between circulating levels of MMP-1, -2, -3, -9, -10, and TIMP-1 and cfPWV (n = 614) as well as office PP (n = 1517). Data on 24-h brachial and 24-h central PP were available in 638 individuals from PROFIL. Analyses were adjusted for age, sex, duration of diabetes, HbA1c, mean arterial pressure (MAP), and eGFR, and additionally for other cardiovascular risk factors and presence of vascular complications. RESULTS: After adjustment for potential confounders and presence of vascular complications, circulating MMP-3 was associated with cfPWV [β per 1 SD higher lnMMP3 0.29 m/s (0.02; 0.55)]. In addition, brachial and central 24-h PP measurements in PROFIL were significantly associated with MMP-2 [(1.40 (0.47:2.33) and 1.43 (0.63:2.23)]. Pooled data analysis showed significant associations of circulating levels of MMP-1 and MMP-2 with office PP [β per 1 SD higher lnMMP-1 and lnMMP-2 = − 0.83 mmHg (95% CI − 1.50; − 0.16) and = 1.33 mmHg (0.55; 2.10), respectively]. CONCLUSIONS: MMPs-1, -2, and -3 are independently associated with markers of arterial stiffening in patients with type 1 diabetes and may become therapeutic targets. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-017-0620-9) contains supplementary material, which is available to authorized users. BioMed Central 2017-10-25 /pmc/articles/PMC5657128/ /pubmed/29070037 http://dx.doi.org/10.1186/s12933-017-0620-9 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Original Investigation
Peeters, Stijn A.
Engelen, Lian
Buijs, Jacqueline
Chaturvedi, Nish
Fuller, John H.
Jorsal, Anders
Parving, Hans-Henrik
Tarnow, Lise
Theilade, Simone
Rossing, Peter
Schalkwijk, Casper G.
Stehouwer, Coen D. A.
Circulating matrix metalloproteinases are associated with arterial stiffness in patients with type 1 diabetes: pooled analysis of three cohort studies
title Circulating matrix metalloproteinases are associated with arterial stiffness in patients with type 1 diabetes: pooled analysis of three cohort studies
title_full Circulating matrix metalloproteinases are associated with arterial stiffness in patients with type 1 diabetes: pooled analysis of three cohort studies
title_fullStr Circulating matrix metalloproteinases are associated with arterial stiffness in patients with type 1 diabetes: pooled analysis of three cohort studies
title_full_unstemmed Circulating matrix metalloproteinases are associated with arterial stiffness in patients with type 1 diabetes: pooled analysis of three cohort studies
title_short Circulating matrix metalloproteinases are associated with arterial stiffness in patients with type 1 diabetes: pooled analysis of three cohort studies
title_sort circulating matrix metalloproteinases are associated with arterial stiffness in patients with type 1 diabetes: pooled analysis of three cohort studies
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5657128/
https://www.ncbi.nlm.nih.gov/pubmed/29070037
http://dx.doi.org/10.1186/s12933-017-0620-9
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