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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3862580?pdf=render |
| _version_ | 1828756705117208576 |
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| author | Helle Wulf-Johansson Sofie Lock Johansson Anders Schlosser Anne Trommelholt Holm Lars Melholt Rasmussen Hans Mickley Axel C P Diederichsen Henrik Munkholm Tina Svenstrup Poulsen Ida Tornøe Vicki Nielsen Niels Marcussen Jørgen Vestbo Susanne Gjørup Sækmose Uffe Holmskov Grith Lykke Sorensen |
| author_facet | Helle Wulf-Johansson Sofie Lock Johansson Anders Schlosser Anne Trommelholt Holm Lars Melholt Rasmussen Hans Mickley Axel C P Diederichsen Henrik Munkholm Tina Svenstrup Poulsen Ida Tornøe Vicki Nielsen Niels Marcussen Jørgen Vestbo Susanne Gjørup Sækmose Uffe Holmskov Grith Lykke Sorensen |
| author_sort | Helle Wulf-Johansson |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T23:21:37Z |
| format | Article |
| id | doaj.art-0444a56474e4417b96cfc70489d6ec38 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T23:21:37Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0444a56474e4417b96cfc70489d6ec382022-12-22T01:29:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8224310.1371/journal.pone.0082243Localization of microfibrillar-associated protein 4 (MFAP4) in human tissues: clinical evaluation of serum MFAP4 and its association with various cardiovascular conditions.Helle Wulf-JohanssonSofie Lock JohanssonAnders SchlosserAnne Trommelholt HolmLars Melholt RasmussenHans MickleyAxel C P DiederichsenHenrik MunkholmTina Svenstrup PoulsenIda TornøeVicki NielsenNiels MarcussenJørgen VestboSusanne Gjørup SækmoseUffe HolmskovGrith Lykke SorensenMicrofibrillar-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.http://europepmc.org/articles/PMC3862580?pdf=render |
| spellingShingle | Helle Wulf-Johansson Sofie Lock Johansson Anders Schlosser Anne Trommelholt Holm Lars Melholt Rasmussen Hans Mickley Axel C P Diederichsen Henrik Munkholm Tina Svenstrup Poulsen Ida Tornøe Vicki Nielsen Niels Marcussen Jørgen Vestbo Susanne Gjørup Sækmose Uffe Holmskov Grith Lykke Sorensen Localization of microfibrillar-associated protein 4 (MFAP4) in human tissues: clinical evaluation of serum MFAP4 and its association with various cardiovascular conditions. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC3862580?pdf=render |
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