Related Experiment Video
Updated: Aug 8, 2026
Isolation of Endocardial and Coronary Endothelial Cells from the Ventricular Free Wall of the Rat Heart
Published on: April 15, 2020
Decreased endomyocardial RANKL expression in transplant coronary artery disease
Thor Ueland1, Lars Gullestad, Svein Simonsen
1Research Institute for Internal Medicine, Rikshospitalet-Radiumhospitalet University Hospital, Oslo, Norway. thor.ueland@medisin.uio.no
Insights
Lower myocardial RANKL expression is linked to transplant-associated coronary artery disease (TxCAD) and acute rejection after heart transplantation (HTx). This suggests RANKL may protect against TxCAD development.
Area of Science:
- Cardiology
- Immunology
- Transplantation Medicine
Background:
- Transplant-associated coronary artery disease (TxCAD) is a significant complication following heart transplantation (HTx).
- Endothelial cell activation and inflammation are key early events in TxCAD pathogenesis.
- Osteoprotegerin (OPG) and receptor activator of nuclear Factor-kappaB ligand (RANKL) are implicated in cardiovascular disease.
Purpose of the Study:
- To investigate the role of OPG and RANKL in the development of TxCAD after HTx.
- To correlate serum and myocardial expression of OPG and RANKL with TxCAD and acute rejection episodes.
Main Methods:
- Serial measurements of serum OPG and RANKL.
- Myocardial gene expression analysis of RANK and RANKL.
- Correlation of mediator levels with TxCAD development and acute rejection within the first year post-HTx.
Main Results:
- Serum OPG and myocardial RANK/OPG expression were highest early post-HTx and decreased over time.
- Myocardial RANKL expression was lower in patients who developed TxCAD or experienced acute rejection.
- No significant changes in serum RANKL were observed.
Conclusions:
- Myocardial RANKL expression, not OPG, may play a protective role in maintaining myocardial and endothelial integrity post-HTx.
- Lower myocardial RANKL levels are associated with increased risk of TxCAD and acute rejection.
- RANKL warrants further investigation as a potential biomarker for predicting TxCAD development.
Abstract:
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.
