Decreased endomyocardial RANKL expression in transplant coronary artery disease.
Transplant-associated coronary artery disease (TxCAD) appears to be initiated by endothelial cell activation and inflammation involving inflammatory cytokines and chemokines. Osteoprotegerin (OPG) and receptor activator of nuclear Factor-kappaB ligand (RANKL) have been implicated in cardiovascular disease progression and we measured the expression of these mediators in serum and myocardial biopsies taken serially during the first year after heart transplantation (HTx), relating them to the development of TxCAD. Serum OPG as well as myocardial gene expression of RANK and OPG, but not RANKL, were highest early after HTx and declined progressively. Importantly, patients who develop TxCAD or experience episodes of acute rejection showed a lower myocardial RANKL expression throughout the first year after transplantation than patients without these complications. Our findings may suggest an unrecognized role RANKL in maintaining myocardial and/or endothelial integrity and suggest that RANKL should be further investigated as a parameter that may predict development of TxCAD.
Ueland
Thor
T
Research Institute for Internal Medicine, Rikshospitalet-Radiumhospitalet University Hospital, Oslo, Norway. thor.ueland@medisin.uio.no
Gullestad
Lars
L
Simonsen
Svein
S
Endresen
Knut
K
Scott
Helge
H
Frøland
Stig S
SS
Geiran
Odd
O
Fiane
Arnt E
AE
Aukrust
Pål
P
D000293:Adolescent; D000328:Adult; D002352:Carrier Proteins / Q000097:blood / Q000378:metabolism*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000378:metabolism*; D005260:Female; D006084:Graft Rejection / Q000378:metabolism; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D013997:Time Factors; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000378:metabolism*
D002352:Carrier Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins