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Increased Levels of Leukocyte-Derived MMP-9 in Patients with Stable Angina Pectoris

OBJECTIVE: There is a growing interest for matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in plasma as novel biomarkers in coronary artery disease (CAD). We aimed to identify the sources of MMP-8, MMP-9, TIMP-1 and TIMP-2 among peripheral blood cells and further explore whether...

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Autores principales: Jönsson, Simon, Lundberg, Anna, Kälvegren, Hanna, Bergström, Ida, Szymanowski, Aleksander, Jonasson, Lena
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084822/
https://www.ncbi.nlm.nih.gov/pubmed/21559401
http://dx.doi.org/10.1371/journal.pone.0019340
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author Jönsson, Simon
Lundberg, Anna
Kälvegren, Hanna
Bergström, Ida
Szymanowski, Aleksander
Jonasson, Lena
author_facet Jönsson, Simon
Lundberg, Anna
Kälvegren, Hanna
Bergström, Ida
Szymanowski, Aleksander
Jonasson, Lena
author_sort Jönsson, Simon
collection PubMed
description OBJECTIVE: There is a growing interest for matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in plasma as novel biomarkers in coronary artery disease (CAD). We aimed to identify the sources of MMP-8, MMP-9, TIMP-1 and TIMP-2 among peripheral blood cells and further explore whether gene expression or protein release was altered in patients with stable angina pectoris (SA). METHODS: In total, plasma MMP-9 was measured in 44 SA patients and 47 healthy controls. From 10 patients and 10 controls, peripheral blood mononuclear cells (PBMC) and neutrophils were isolated and stimulated ex vivo. MMPs, TIMPs and myeloperoxidase were measured in plasma and supernatants by ELISA. The corresponding gene expression was measured by real-time PCR. RESULTS: Neutrophils were the dominant source of MMP-8 and MMP-9. Upon moderate stimulation with IL-8, the neutrophil release of MMP-9 was higher in the SA patients compared with controls (p<0.05). In PBMC, the TIMP-1 and MMP-9 mRNA expression was higher in SA patients compared with controls, p<0.01 and 0.05, respectively. There were no differences in plasma levels between patients and controls except for TIMP-2, which was lower in patients, p<0.01. CONCLUSION: Measurements of MMPs and TIMPs in plasma may be of limited use. Despite similar plasma levels in SA patients and controls, the leukocyte-derived MMP-9 and TIMP-1 are significantly altered in patients. The findings indicate that the leukocytes are more prone to release and produce MMP-9 in symptomatic and angiographically verified CAD—a phenomenon that may have clinical implications in the course of disease.
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spelling pubmed-30848222011-05-10 Increased Levels of Leukocyte-Derived MMP-9 in Patients with Stable Angina Pectoris Jönsson, Simon Lundberg, Anna Kälvegren, Hanna Bergström, Ida Szymanowski, Aleksander Jonasson, Lena PLoS One Research Article OBJECTIVE: There is a growing interest for matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in plasma as novel biomarkers in coronary artery disease (CAD). We aimed to identify the sources of MMP-8, MMP-9, TIMP-1 and TIMP-2 among peripheral blood cells and further explore whether gene expression or protein release was altered in patients with stable angina pectoris (SA). METHODS: In total, plasma MMP-9 was measured in 44 SA patients and 47 healthy controls. From 10 patients and 10 controls, peripheral blood mononuclear cells (PBMC) and neutrophils were isolated and stimulated ex vivo. MMPs, TIMPs and myeloperoxidase were measured in plasma and supernatants by ELISA. The corresponding gene expression was measured by real-time PCR. RESULTS: Neutrophils were the dominant source of MMP-8 and MMP-9. Upon moderate stimulation with IL-8, the neutrophil release of MMP-9 was higher in the SA patients compared with controls (p<0.05). In PBMC, the TIMP-1 and MMP-9 mRNA expression was higher in SA patients compared with controls, p<0.01 and 0.05, respectively. There were no differences in plasma levels between patients and controls except for TIMP-2, which was lower in patients, p<0.01. CONCLUSION: Measurements of MMPs and TIMPs in plasma may be of limited use. Despite similar plasma levels in SA patients and controls, the leukocyte-derived MMP-9 and TIMP-1 are significantly altered in patients. The findings indicate that the leukocytes are more prone to release and produce MMP-9 in symptomatic and angiographically verified CAD—a phenomenon that may have clinical implications in the course of disease. Public Library of Science 2011-04-29 /pmc/articles/PMC3084822/ /pubmed/21559401 http://dx.doi.org/10.1371/journal.pone.0019340 Text en Jönsson et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Jönsson, Simon
Lundberg, Anna
Kälvegren, Hanna
Bergström, Ida
Szymanowski, Aleksander
Jonasson, Lena
Increased Levels of Leukocyte-Derived MMP-9 in Patients with Stable Angina Pectoris
title Increased Levels of Leukocyte-Derived MMP-9 in Patients with Stable Angina Pectoris
title_full Increased Levels of Leukocyte-Derived MMP-9 in Patients with Stable Angina Pectoris
title_fullStr Increased Levels of Leukocyte-Derived MMP-9 in Patients with Stable Angina Pectoris
title_full_unstemmed Increased Levels of Leukocyte-Derived MMP-9 in Patients with Stable Angina Pectoris
title_short Increased Levels of Leukocyte-Derived MMP-9 in Patients with Stable Angina Pectoris
title_sort increased levels of leukocyte-derived mmp-9 in patients with stable angina pectoris
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084822/
https://www.ncbi.nlm.nih.gov/pubmed/21559401
http://dx.doi.org/10.1371/journal.pone.0019340
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