Aortic valve disease and gamma-glutamyltransferase: Accumulation in tissue and relationships with calcific degeneration
Aortic valve disease and gamma-glutamyltransferase: Accumulation in tissue and relationships with calcific degeneration
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DOI：
10.1016/j.atherosclerosis.2010.08.063
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发表时间：
2010-12-01
期刊：
影响因子：
5.3
通讯作者：
Tanganelli, Piero
中科院分区：
文献类型：
--
作者：
Cappelli, Stefania;Epistolato, Maria Carmela;Tanganelli, Piero
目的：退行性主动脉瓣病具有动脉粥样硬化病变的某些组织学特征。近年来，γ-谷氨酰转移酶(GGT)参与了动脉粥样硬化的发病机制，并参与了钙代谢相关细胞的调节。目的：探讨该酶活性在主动脉瓣病变中的意义。方法：应用免疫组织化学方法对瓣膜狭窄患者瓣膜置换术患者的瓣叶进行GGT免疫组织化学染色。结果：组织细胞外GGT染色与脂质沉积密切相关(p<；0.0001)。GGT由新生血管周围的CD68阳性细胞和邻近骨化生区域的MMP9和TRAP阳性的多核细胞表达。血浆总GGT水平与低高密度脂蛋白胆固醇(p=0.028)和高甘油三酯(p=0.017)相关。组织中总GGT活性与瓣膜钙化程度呈负相关(p=0.03)。血清和组织GGT水平与瓣膜狭窄的严重程度呈负相关，根据跨瓣压差峰值(分别为P<；0.0003和P<；0.002)判断。结论：GGT活性在瓣叶脂质成分中的积聚可能是动脉粥样硬化和退行性主动脉瓣病变形成的共同机制。此外，GGT在具有破骨细胞样表型的细胞中的表达，以及它与瓣膜钙化和瓣膜狭窄程度的负相关，为最近提出的GGT参与钙化组织的动态平衡提供了额外的支持。(C)2010爱思唯尔爱尔兰有限公司。保留所有权利。
Objective: Degenerative aortic valve disease is characterized by some of the histological features of atherosclerotic lesions. Gamma-glutamyltransferase (GGT) has been recently implicated in pathogenesis of atherosclerosis, as well as in modulation of cells involved in calcium metabolism. We aimed to evaluate the possible implication of this enzyme activity in aortic valve disease.Methods: GGT immunohistochemistry was performed on valve leaflets of 64 patients with aortic valve stenosis undergoing valve replacement. Fractional GGT activity in plasma and tissue was analysed in a subgroup of cases by molecular exclusion chromatography.Results: A close association was found between tissue extracellular GGT staining and lipid deposits (p < 0.0001). GGT was expressed by CD68-positive cells around neovessels, as well as by MMP-9- and TRAP-positive multinucleated cells in the vicinity of bone metaplasia areas. Total plasma GGT levels were associated with low HDL-c (p = 0.028) and high triglycerides (p = 0.017). Total GGT activity in tissue was negatively correlated with the extent of valves calcification (p = 0.03). Both serum and tissue GGT levels were negatively associated with severity of valve stenosis, as judged by peak transvalvular pressure gradients (p < 0.0003 and p < 0.002, respectively).Conclusions: Accumulation of GGT activity inside the lipid component of valves leaflets suggests a common mechanism of lesion shaping underlying both atherosclerosis and degenerative aortic valve disease. Moreover, the finding of GGT expression in cells with an osteoclast-like phenotype, and its negative correlation with both valves calcification and degree of valvular stenosis lend additional support to the recently envisaged involvement of GGT in the homeostasis of calcified tissues. (C) 2010 Elsevier Ireland Ltd. All rights reserved.