RANKL Expression Is Increased in Circulating Mononuclear Cells of Patients with Calcific Aortic Stenosis.
Marcello RattazziElisabetta FagginElisa BertaccoRoberta BusoMassimo PuatoMario PlebaniMartina ZaninottoDavide CondottaGiacomo ZoppellaroLeopoldo PaglianiGiuseppe TarantiniSabino IlicetoElisa CovoloGiuseppe FaggianFrancesco OnoratiMikhail DodonovAlessandro DaniottiPaola PantanoZoran OlivariGiovanni BenfariPaolo PaulettoPublished in: Journal of cardiovascular translational research (2018)
We aimed to investigate whether the expression of the OPG/RANK/RANKL triad in peripheral blood mononuclear cells (PBMC) and circulating levels of markers of ectopic mineralization (OPG, FGF-23, PPi) are modified in patients with calcific aortic valve disease (CAVD). We found that patients affected by CAVD (n = 50) had significantly higher circulating levels of OPG as compared to control individuals (p = 0.003). No differences between the two groups were found in FGF-23 and PPi levels. RANKL expression was higher in the PBMC from CAVD patients (p = 0.018) and was directly correlated with the amount of valve calcification (p = 0.032). In vitro studies showed that treatment of valve interstitial cells (VIC) with RANKL plus phosphate was followed by increase in matrix mineralization (p = 0.001). In conclusion, RANKL expression is increased in PBMC of patients with CAVD, is directly correlated with the degree of valve calcification, and promotes pro-calcific differentiation of VIC.
Keyphrases
- aortic valve
- aortic stenosis
- ejection fraction
- transcatheter aortic valve replacement
- aortic valve replacement
- transcatheter aortic valve implantation
- poor prognosis
- induced apoptosis
- newly diagnosed
- nuclear factor
- mitral valve
- prognostic factors
- bone loss
- heart failure
- binding protein
- cell cycle arrest
- immune response
- atrial fibrillation
- endoplasmic reticulum stress
- long non coding rna
- cell death
- oxidative stress
- patient reported
- replacement therapy