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Localization of Microfibrillar-Associated Protein 4 (MFAP4) in Human Tissues: Clinical Evaluation of Serum MFAP4 and Its Association with Various Cardiovascular Conditions

Microfibrillar-associated protein 4 (MFAP4) is located in the extracellular matrix (ECM). We sought to identify tissues with high levels of MFAP4 mRNA and MFAP4 protein expression. Moreover, we aimed to evaluate the significance of MFAP4 as a marker of cardiovascular disease (CVD) and to correlate M...

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Autores principales: Wulf-Johansson, Helle, Lock Johansson, Sofie, Schlosser, Anders, Trommelholt Holm, Anne, Melholt Rasmussen, Lars, Mickley, Hans, Diederichsen, Axel C. P., Munkholm, Henrik, Poulsen, Tina Svenstrup, Tornøe, Ida, Nielsen, Vicki, Marcussen, Niels, Vestbo, Jørgen, Sækmose, Susanne Gjørup, Holmskov, Uffe, Sorensen, Grith Lykke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3862580/
https://www.ncbi.nlm.nih.gov/pubmed/24349233
http://dx.doi.org/10.1371/journal.pone.0082243
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author Wulf-Johansson, Helle
Lock Johansson, Sofie
Schlosser, Anders
Trommelholt Holm, Anne
Melholt Rasmussen, Lars
Mickley, Hans
Diederichsen, Axel C. P.
Munkholm, Henrik
Poulsen, Tina Svenstrup
Tornøe, Ida
Nielsen, Vicki
Marcussen, Niels
Vestbo, Jørgen
Sækmose, Susanne Gjørup
Holmskov, Uffe
Sorensen, Grith Lykke
author_facet Wulf-Johansson, Helle
Lock Johansson, Sofie
Schlosser, Anders
Trommelholt Holm, Anne
Melholt Rasmussen, Lars
Mickley, Hans
Diederichsen, Axel C. P.
Munkholm, Henrik
Poulsen, Tina Svenstrup
Tornøe, Ida
Nielsen, Vicki
Marcussen, Niels
Vestbo, Jørgen
Sækmose, Susanne Gjørup
Holmskov, Uffe
Sorensen, Grith Lykke
author_sort Wulf-Johansson, Helle
collection PubMed
description Microfibrillar-associated protein 4 (MFAP4) is located in the extracellular matrix (ECM). We sought to identify tissues with high levels of MFAP4 mRNA and MFAP4 protein expression. Moreover, we aimed to evaluate the significance of MFAP4 as a marker of cardiovascular disease (CVD) and to correlate MFAP4 with other known ECM markers, such as fibulin-1, osteoprotegerin (OPG), and osteopontin (OPN). Quantitative real-time PCR demonstrated that MFAP4 mRNA was more highly expressed in the heart, lung, and intestine than in other elastic tissues. Immunohistochemical studies demonstrated high levels of MFAP4 protein mainly at sites rich in elastic fibers and within blood vessels in all tissues investigated. The AlphaLISA technique was used to determine serum MFAP4 levels in a clinical cohort of 172 patients consisting of 5 matched groups with varying degrees of CVD: 1: patients with ST elevation myocardial infarction (STEMI), 2: patients with non-STEMI, 3: patients destined for vascular surgery because of various atherosclerotic diseases (stable atherosclerotic disease), 4: apparently healthy individuals with documented coronary artery calcification (CAC-positive), and 5: apparently healthy individuals without signs of coronary artery calcification (CAC-negative). Serum MFAP4 levels were significantly lower in patients with stable atherosclerotic disease than CAC-negative individuals (p<0.05). Furthermore, lower serum MFAP4 levels were present in patients with stable atherosclerotic disease compared with STEMI and non-STEMI patients (p<0.05). In patients with stable atherosclerotic disease, positive correlations between MFAP4 and both fibulin-1 (ρ = 0.50; p = 0.0244) and OPG (ρ = 0.62; p = 0.0014) were found. Together, these results indicate that MFAP4 is mainly located in elastic fibers and is highly expressed in blood vessels. The present study suggests that serum MFAP4 varies in groups of patients with different cardiovascular conditions. Further studies are warranted to describe the role of serum MFAP4 as a biomarker of stable atherosclerotic disease.
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spelling pubmed-38625802013-12-17 Localization of Microfibrillar-Associated Protein 4 (MFAP4) in Human Tissues: Clinical Evaluation of Serum MFAP4 and Its Association with Various Cardiovascular Conditions Wulf-Johansson, Helle Lock Johansson, Sofie Schlosser, Anders Trommelholt Holm, Anne Melholt Rasmussen, Lars Mickley, Hans Diederichsen, Axel C. P. Munkholm, Henrik Poulsen, Tina Svenstrup Tornøe, Ida Nielsen, Vicki Marcussen, Niels Vestbo, Jørgen Sækmose, Susanne Gjørup Holmskov, Uffe Sorensen, Grith Lykke PLoS One Research Article Microfibrillar-associated protein 4 (MFAP4) is located in the extracellular matrix (ECM). We sought to identify tissues with high levels of MFAP4 mRNA and MFAP4 protein expression. Moreover, we aimed to evaluate the significance of MFAP4 as a marker of cardiovascular disease (CVD) and to correlate MFAP4 with other known ECM markers, such as fibulin-1, osteoprotegerin (OPG), and osteopontin (OPN). Quantitative real-time PCR demonstrated that MFAP4 mRNA was more highly expressed in the heart, lung, and intestine than in other elastic tissues. Immunohistochemical studies demonstrated high levels of MFAP4 protein mainly at sites rich in elastic fibers and within blood vessels in all tissues investigated. The AlphaLISA technique was used to determine serum MFAP4 levels in a clinical cohort of 172 patients consisting of 5 matched groups with varying degrees of CVD: 1: patients with ST elevation myocardial infarction (STEMI), 2: patients with non-STEMI, 3: patients destined for vascular surgery because of various atherosclerotic diseases (stable atherosclerotic disease), 4: apparently healthy individuals with documented coronary artery calcification (CAC-positive), and 5: apparently healthy individuals without signs of coronary artery calcification (CAC-negative). Serum MFAP4 levels were significantly lower in patients with stable atherosclerotic disease than CAC-negative individuals (p<0.05). Furthermore, lower serum MFAP4 levels were present in patients with stable atherosclerotic disease compared with STEMI and non-STEMI patients (p<0.05). In patients with stable atherosclerotic disease, positive correlations between MFAP4 and both fibulin-1 (ρ = 0.50; p = 0.0244) and OPG (ρ = 0.62; p = 0.0014) were found. Together, these results indicate that MFAP4 is mainly located in elastic fibers and is highly expressed in blood vessels. The present study suggests that serum MFAP4 varies in groups of patients with different cardiovascular conditions. Further studies are warranted to describe the role of serum MFAP4 as a biomarker of stable atherosclerotic disease. Public Library of Science 2013-12-13 /pmc/articles/PMC3862580/ /pubmed/24349233 http://dx.doi.org/10.1371/journal.pone.0082243 Text en © 2013 Wulf-Johansson 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
Wulf-Johansson, Helle
Lock Johansson, Sofie
Schlosser, Anders
Trommelholt Holm, Anne
Melholt Rasmussen, Lars
Mickley, Hans
Diederichsen, Axel C. P.
Munkholm, Henrik
Poulsen, Tina Svenstrup
Tornøe, Ida
Nielsen, Vicki
Marcussen, Niels
Vestbo, Jørgen
Sækmose, Susanne Gjørup
Holmskov, Uffe
Sorensen, Grith Lykke
Localization of Microfibrillar-Associated Protein 4 (MFAP4) in Human Tissues: Clinical Evaluation of Serum MFAP4 and Its Association with Various Cardiovascular Conditions
title Localization of Microfibrillar-Associated Protein 4 (MFAP4) in Human Tissues: Clinical Evaluation of Serum MFAP4 and Its Association with Various Cardiovascular Conditions
title_full Localization of Microfibrillar-Associated Protein 4 (MFAP4) in Human Tissues: Clinical Evaluation of Serum MFAP4 and Its Association with Various Cardiovascular Conditions
title_fullStr Localization of Microfibrillar-Associated Protein 4 (MFAP4) in Human Tissues: Clinical Evaluation of Serum MFAP4 and Its Association with Various Cardiovascular Conditions
title_full_unstemmed Localization of Microfibrillar-Associated Protein 4 (MFAP4) in Human Tissues: Clinical Evaluation of Serum MFAP4 and Its Association with Various Cardiovascular Conditions
title_short Localization of Microfibrillar-Associated Protein 4 (MFAP4) in Human Tissues: Clinical Evaluation of Serum MFAP4 and Its Association with Various Cardiovascular Conditions
title_sort localization of microfibrillar-associated protein 4 (mfap4) in human tissues: clinical evaluation of serum mfap4 and its association with various cardiovascular conditions
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3862580/
https://www.ncbi.nlm.nih.gov/pubmed/24349233
http://dx.doi.org/10.1371/journal.pone.0082243
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