TY - JOUR
T1 - High levels of osteoprotegerin are associated with coronary artery calcification in patients suspected of a chronic coronary syndrome
AU - Dekker, Mirthe
AU - Waissi, Farahnaz
AU - Silvis, Max J.M.
AU - Bennekom, Joelle V.
AU - Schoneveld, Arjan H.
AU - de Winter, Robbert J.
AU - Isgum, Ivana
AU - Lessmann, Nikolas
AU - Velthuis, Birgitta K.
AU - Pasterkamp, Gerard
AU - Mosterd, Arend
AU - Timmers, Leo
AU - de Kleijn, Dominique P.V.
N1 - Funding Information:
This study was funded by research Grants from the Dutch Heart Foundation (CVON 2017-05 pERSUASIVE and NHS Grant 2017T067).
Publisher Copyright:
© 2021, The Author(s).
© 2021. The Author(s).
PY - 2021/9/23
Y1 - 2021/9/23
N2 - Plasma osteoprotegerin (OPG) and vascular smooth muscle cell (VSMC) derived extracellular vesicles (EVs) are important regulators in the process of vascular calcification (VC). In population studies, high levels of OPG are associated with events. In animal studies, however, high OPG levels result in reduction of VC. VSMC-derived EVs are assumed to be responsible for OPG transport and VC but this role has not been studied. For this, we investigated the association between OPG in plasma and circulating EVs with coronary artery calcium (CAC) as surrogate for VC in symptomatic patients. We retrospectively assessed 742 patients undergoing myocardial perfusion imaging (MPI). CAC scores were determined on the MPI-CT images using a previously developed automated algorithm. Levels of OPG were quantified in plasma and two EV-subpopulations (LDL and TEX), using an electrochemiluminescence immunoassay. Circulating levels of OPG were independently associated with CAC scores in plasma; OR 1.39 (95% CI 1.17–1.65), and both EV populations; EV-LDL; OR 1.51 (95% CI 1.27–1.80) and EV-TEX; OR 1.21 (95% CI 1.02–1.42). High levels of OPG in plasma were independently associated with CAC scores in this symptomatic patient cohort. High levels of EV-derived OPG showed the same positive association with CAC scores, suggesting that EV-derived OPG mirrors the same pathophysiological process as plasma OPG.
AB - Plasma osteoprotegerin (OPG) and vascular smooth muscle cell (VSMC) derived extracellular vesicles (EVs) are important regulators in the process of vascular calcification (VC). In population studies, high levels of OPG are associated with events. In animal studies, however, high OPG levels result in reduction of VC. VSMC-derived EVs are assumed to be responsible for OPG transport and VC but this role has not been studied. For this, we investigated the association between OPG in plasma and circulating EVs with coronary artery calcium (CAC) as surrogate for VC in symptomatic patients. We retrospectively assessed 742 patients undergoing myocardial perfusion imaging (MPI). CAC scores were determined on the MPI-CT images using a previously developed automated algorithm. Levels of OPG were quantified in plasma and two EV-subpopulations (LDL and TEX), using an electrochemiluminescence immunoassay. Circulating levels of OPG were independently associated with CAC scores in plasma; OR 1.39 (95% CI 1.17–1.65), and both EV populations; EV-LDL; OR 1.51 (95% CI 1.27–1.80) and EV-TEX; OR 1.21 (95% CI 1.02–1.42). High levels of OPG in plasma were independently associated with CAC scores in this symptomatic patient cohort. High levels of EV-derived OPG showed the same positive association with CAC scores, suggesting that EV-derived OPG mirrors the same pathophysiological process as plasma OPG.
UR - http://www.scopus.com/inward/record.url?scp=85115392018&partnerID=8YFLogxK
U2 - 10.1038/s41598-021-98177-4
DO - 10.1038/s41598-021-98177-4
M3 - Article
C2 - 34556709
AN - SCOPUS:85115392018
SN - 2045-2322
VL - 11
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 18946
ER -