PMID- 24349233
OWN - NLM
STAT- MEDLINE
DCOM- 20141012
LR  - 20220408
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 12
DP  - 2013
TI  - Localization of microfibrillar-associated protein 4 (MFAP4) in human tissues: 
      clinical evaluation of serum MFAP4 and its association with various 
      cardiovascular conditions.
PG  - e82243
LID - 10.1371/journal.pone.0082243 [doi]
LID - e82243
AB  - 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 (rho = 0.50; p = 0.0244) and OPG (rho = 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.
FAU - Wulf-Johansson, Helle
AU  - Wulf-Johansson H
AD  - Cardiovascular and Renal Research, Institute of Molecular Medicine, University of 
      Southern Denmark, Odense, Denmark.
FAU - Lock Johansson, Sofie
AU  - Lock Johansson S
AD  - Cardiovascular and Renal Research, Institute of Molecular Medicine, University of 
      Southern Denmark, Odense, Denmark.
FAU - Schlosser, Anders
AU  - Schlosser A
AD  - Cardiovascular and Renal Research, Institute of Molecular Medicine, University of 
      Southern Denmark, Odense, Denmark.
FAU - Trommelholt Holm, Anne
AU  - Trommelholt Holm A
AD  - Cardiovascular and Renal Research, Institute of Molecular Medicine, University of 
      Southern Denmark, Odense, Denmark.
FAU - Rasmussen, Lars Melholt
AU  - Rasmussen LM
AD  - Cardiovascular and Renal Research, Institute of Molecular Medicine, University of 
      Southern Denmark, Odense, Denmark ; Centre for Individualized Medicine in 
      Arterial Diseases (CIMA), Department of Clinical Biochemistry and Pharmacology, 
      Odense University Hospital, Odense, Denmark ; Odense Patient data Explorative 
      Network (OPEN), Odense University Hospital, Odense, Denmark.
FAU - Mickley, Hans
AU  - Mickley H
AD  - Odense Patient data Explorative Network (OPEN), Odense University Hospital, 
      Odense, Denmark ; Department of Cardiology, Odense University Hospital, Odense, 
      Denmark.
FAU - Diederichsen, Axel C P
AU  - Diederichsen AC
AD  - Odense Patient data Explorative Network (OPEN), Odense University Hospital, 
      Odense, Denmark ; Department of Cardiology, Odense University Hospital, Odense, 
      Denmark.
FAU - Munkholm, Henrik
AU  - Munkholm H
AD  - Department of Cardiology, Lillebaelt Hospital Vejle, Vejle, Denmark.
FAU - Poulsen, Tina Svenstrup
AU  - Poulsen TS
AD  - Department of Cardiology, Odense University Hospital, Odense, Denmark.
FAU - Tornoe, Ida
AU  - Tornoe I
AD  - Cardiovascular and Renal Research, Institute of Molecular Medicine, University of 
      Southern Denmark, Odense, Denmark.
FAU - Nielsen, Vicki
AU  - Nielsen V
AD  - Cardiovascular and Renal Research, Institute of Molecular Medicine, University of 
      Southern Denmark, Odense, Denmark.
FAU - Marcussen, Niels
AU  - Marcussen N
AD  - Department of Clinical Pathology, Odense University Hospital, Odense, Denmark.
FAU - Vestbo, Jorgen
AU  - Vestbo J
AD  - Department of Respiratory Medicine, Odense University Hospital, Odense, Denmark ; 
      Respiratory and Allergy Research Group, Manchester Academic Health Sciences 
      Centre, University Hospital South Manchester NHS Foundation Trust, Manchester, 
      United Kingdom.
FAU - Saekmose, Susanne Gjorup
AU  - Saekmose SG
AD  - Cardiovascular and Renal Research, Institute of Molecular Medicine, University of 
      Southern Denmark, Odense, Denmark ; Department of Clinical Immunology, Naestved 
      Hospital, Naestved, Denmark.
FAU - Holmskov, Uffe
AU  - Holmskov U
AD  - Cardiovascular and Renal Research, Institute of Molecular Medicine, University of 
      Southern Denmark, Odense, Denmark.
FAU - Sorensen, Grith Lykke
AU  - Sorensen GL
AD  - Cardiovascular and Renal Research, Institute of Molecular Medicine, University of 
      Southern Denmark, Odense, Denmark.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131213
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Carrier Proteins)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (MFAP4 protein, human)
RN  - 0 (Osteoprotegerin)
RN  - 0 (RNA, Messenger)
RN  - 106441-73-0 (Osteopontin)
SB  - IM
MH  - Aged
MH  - Animals
MH  - Cardiovascular Diseases/*blood/genetics/pathology
MH  - Carrier Proteins/*blood/genetics
MH  - Demography
MH  - Elastic Tissue/metabolism
MH  - Extracellular Matrix Proteins/*blood/genetics
MH  - Female
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation
MH  - Glycoproteins/*blood/genetics
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Middle Aged
MH  - Myocardial Infarction/blood/genetics/pathology
MH  - *Organ Specificity/genetics
MH  - Osteopontin/blood
MH  - Osteoprotegerin/blood
MH  - Protein Transport
MH  - RNA, Messenger/genetics/metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Statistics, Nonparametric
PMC - PMC3862580
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/12/19 06:00
MHDA- 2014/10/13 06:00
PMCR- 2013/12/13
CRDT- 2013/12/19 06:00
PHST- 2013/07/30 00:00 [received]
PHST- 2013/10/21 00:00 [accepted]
PHST- 2013/12/19 06:00 [entrez]
PHST- 2013/12/19 06:00 [pubmed]
PHST- 2014/10/13 06:00 [medline]
PHST- 2013/12/13 00:00 [pmc-release]
AID - PONE-D-13-31492 [pii]
AID - 10.1371/journal.pone.0082243 [doi]
PST - epublish
SO  - PLoS One. 2013 Dec 13;8(12):e82243. doi: 10.1371/journal.pone.0082243. 
      eCollection 2013.