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

Helle Wulf-Johansson, Sofie Lock Johansson, Anders Schlosser, Anne Trommelholt Holm, Lars Melholt Rasmussen, Hans Mickley, Axel Cosmus Pyndt Diederichsen, Henrik Munkholm, Tina Svenstrup Poulsen, Ida Tornøe, Vicki Nielsen, Niels Marcussen, Jørgen Vestbo, Susanne Gjørup Sækmose, Uffe Holmskov, Grith Lykke Sorensen

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Abstrakt

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
OriginalsprogEngelsk
Artikelnummere82243
TidsskriftPLOS ONE
Vol/bind8
Udgave nummer12
Antal sider11
ISSN1932-6203
DOI
StatusUdgivet - 2013

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