Nagy Edit, Eriksson Per, Yousry Mohamed, Caidahl Kenneth, Ingelsson Erik, Hansson Göran K, Franco-Cereceda Anders, Bäck Magnus
Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
Int J Cardiol. 2013 Oct 3;168(3):2264-71. doi: 10.1016/j.ijcard.2013.01.207. Epub 2013 Feb 27.
Bone remodeling in calcified aortic valves is thought to originate from microfractures at multiple sites of the valve, at which osteoclasts and osteoblasts are recruited. The aim of the present study was to assess circulating mediators of bone homeostasis, correlate them to the severity of stenosis and explore the spatio-temporal distribution of bone turnover in different parts of calcified aortic valve tissue.
Plasma and explanted aortic valves were obtained from 46 patients undergoing aortic valve replacement surgery. Plasma levels of tartrate-resistant acid phosphatase (TRAP), receptor activator of nuclear-κB (RANK) ligand and Runt-related transcription factor 2 (Runx2/Cbfa1) exhibited a significant correlation to the severity of aortic stenosis. mRNA levels in normal, thickened and calcified parts of aortic valves assessed by quantitative real-time PCR were significantly elevated in calcified parts of valves for TRAP (5.08 ± 1.6-fold, P<0.001) RANK ligand (8.6 ± 4.2-fold, P<0.001) and RANK (1.98 ± 0.78-fold, P=0.015). In an age, gender and aortic valve anatomy-adjusted multivariable regression analysis the local transcript levels of TRAP correlated significantly with echocardiographic parameters quantifying stenosis severity in early stages, whereas the expression level of Runx2/Cbfa1 was a predictor of the stenosis severity in advanced stages.
These findings suggest a critical role of bone turnover as a determinant of aortic stenosis severity.
钙化主动脉瓣中的骨重塑被认为起源于瓣膜多个部位的微骨折，破骨细胞和成骨细胞在这些部位被募集。本研究的目的是评估骨稳态的循环介质，将它们与狭窄严重程度相关联，并探索钙化主动脉瓣组织不同部位骨转换的时空分布。
从46例行主动脉瓣置换手术的患者中获取血浆和离体主动脉瓣。抗酒石酸酸性磷酸酶（TRAP）、核因子κB受体活化因子（RANK）配体和Runx2/Cbfa1的血浆水平与主动脉狭窄的严重程度呈显著相关。通过定量实时PCR评估的主动脉瓣正常、增厚和钙化部分的mRNA水平，在瓣膜钙化部分中，TRAP（5.08±1.6倍，P<0.001）、RANK配体（8.6±4.2倍，P<0.001）和RANK（1.98±0.78倍，P=0.015）显著升高。在年龄、性别和主动脉瓣解剖结构调整后的多变量回归分析中，TRAP的局部转录水平与早期量化狭窄严重程度的超声心动图参数显著相关，而Runx2/Cbfa1的表达水平是晚期狭窄严重程度的预测指标。
这些发现表明骨转换作为主动脉狭窄严重程度的决定因素起着关键作用。
