Serum levels of the osteoprotegerin, receptor activator of nuclear factor kappa-B ligand, metalloproteinase-1 (MMP-1) and tissue inhibitors of MMP-1 levels are increased in men 6 months after acute myocardial infarction.
BACKGROUND
Osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) are critical regulators of bone remodeling and RANKL/RANK signaling could also play an important role in the remodeling process of several tissues, such as myocardium. Therefore, we investigated whether the serum concentrations of OPG and RANKL correlate with the serum levels of metalloproteinase-1 (MMP-1), MMP-9 and tissue inhibitors of MMP-1 (TIMP-1), which are known regulators of myocardial healing in acute myocardial infarction (AMI) patients.


METHODS
We analyzed blood samples from 51 consecutively hospitalized men with AMI, 12 men with established ischemic heart failure (New York Heart Association category II, NYHA-II) and 12 healthy men age-matched to the NYHA-II patients. Serum levels of MMP-1, MMP-9, TIMP-1, OPG and RANKL were quantified using commercially available ELISA kits. AMI patients were sampled 4 days and 6 months after MI.


RESULTS
Our data revealed increased serum levels of OPG, RANKL, MMP-1 and TIMP-1 levels and significant correlations between increased RANKL levels and MMP-1 and TIMP-1 serum levels 6 months after MI. In addition, the ratio OPG/RANKL was very low 6 months after MI, suggesting that the nuclear factor kappa-B signaling is possibly more active 6 months post-MI than it is on day 4 post-MI.


CONCLUSIONS
Our data suggest that OPG, RANKL, MMP-1 and TIMP-1 serum levels can be potential mediators of myocardial healing after MI. However, further large studies are needed to confirm the utility of OPG and RANKL as markers of healing after ST elevation in MI.
Halapas
Antonios
A
Department of Experimental Physiology, Medical School, University of Athens, Athens, Greece.
Zacharoulis
Achilleas
A
Theocharis
Stamatios
S
Karavidas
Apostolos
A
Korres
Dimitrios
D
Papadopoulos
Kostantinos
K
Katopodis
Harris
H
Stavropoulou
Anastasia
A
Lembessis
Peter
P
Xiromeritis
Costas
C
Zacharoulis
Apostolos
A
Koutsilieris
Michael
M
D000208:Acute Disease; D000368:Aged; D001774:Blood Chemical Analysis / Q000379:methods*; D016022:Case-Control Studies; D004452:Echocardiography / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood*; D053244:Osteoprotegerin / Q000097:blood*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000097:blood*; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
D053244:Osteoprotegerin; D053246:Receptor Activator of Nuclear Factor-kappa B; D019715:Tissue Inhibitor of Metalloproteinase-1; D020781:Matrix Metalloproteinase 1