Franzini Maria, Corti Alessandro, Martinelli Barbara, Del Corso Antonella, Emdin Michele, Parenti Giuliano F, Glauber Mattia, Pompella Alfonso, Paolicchi Aldo
Department of Experimental Pathology BMIE, University of Pisa Medical School, Via Roma 55, 56126 Pisa, Italy.
Atherosclerosis. 2009 Jan;202(1):119-27. doi: 10.1016/j.atherosclerosis.2008.03.023. Epub 2008 Apr 11.
Serum gamma-glutamyltransferase (GGT) activity has been identified as a predictor of complications of atherosclerosis, with a prognostic value for cardiovascular diseases and stroke. Human atherosclerotic lesions contain active GGT, which can give rise to pro-oxidant molecular species; thus a direct contribution of GGT to atherosclerosis progression is conceivable. The relationship between plaque and serum GGT is however unclear.
Human carotid plaques obtained from 18 consecutive patients undergoing carotid endoarteriectomy were analyzed, of which 6 were used for anion exchange and gel filtration chromatography/western blot studies, 7 for beta-lipoprotein precipitation, and 5 for RNA extraction and determination of low molecular weight thiols. Mean GGT activity in crude plaque homogenates was 60.9+/-21.5 (S.D.) mU/g tissue. The characteristics of GGT activity were compared in plaque homogenates and in serum obtained from controls (healthy blood donors). The methods employed (anion exchange and gel chromatography, western blot) showed the presence in plaque homogenates of two distinct complexes containing GGT activity, one of which comparable with plasma LDL/GGT complexes. Accordingly, precipitation of beta-lipoproteins from plaque homogenates resulted in removal of GGT activity. RT-PCR indicated in plaques the presence of GGT mRNA transcribed from GGT-I gene. Analysis of plaque extracts also revealed the presence of enzyme product cysteinyl-glycine both as free and protein-bound form, confirming that GGT-dependent pro-oxidant reactions may occur within the plaque environment.
The results obtained suggest the presence in plaques of a serum-like GGT protein, indicating that a direct contribution of serum GGT to enzyme activity found within atherosclerotic lesions is possible. Data also indicate the occurrence of GGT-mediated redox reactions within plaque environment, which might influence plaque progression.
血清γ-谷氨酰转移酶（GGT）活性已被确定为动脉粥样硬化并发症的预测指标，对心血管疾病和中风具有预后价值。人类动脉粥样硬化病变中含有活性GGT，其可产生促氧化分子物质；因此，可以想象GGT对动脉粥样硬化进展有直接作用。然而，斑块与血清GGT之间的关系尚不清楚。
对连续18例接受颈动脉内膜切除术患者的人颈动脉斑块进行分析，其中6例用于阴离子交换和凝胶过滤色谱/蛋白质印迹研究，7例用于β-脂蛋白沉淀，5例用于RNA提取和低分子量硫醇的测定。斑块粗提物匀浆中的平均GGT活性为60.9±21.5（标准差）mU/g组织。比较了斑块匀浆和对照组（健康献血者）血清中GGT活性的特征。所采用的方法（阴离子交换和凝胶色谱、蛋白质印迹）显示斑块匀浆中存在两种含有GGT活性的不同复合物，其中一种与血浆低密度脂蛋白/GGT复合物相当。因此，从斑块匀浆中沉淀β-脂蛋白可导致GGT活性去除。逆转录-聚合酶链反应表明斑块中存在从GGT-I基因转录的GGT mRNA。对斑块提取物的分析还显示，酶产物半胱氨酰甘氨酸以游离和蛋白质结合形式存在，证实GGT依赖性促氧化反应可能在斑块环境中发生。
所得结果表明斑块中存在类似血清的GGT蛋白，表明血清GGT可能对动脉粥样硬化病变中的酶活性有直接作用。数据还表明在斑块环境中发生了GGT介导的氧化还原反应，这可能影响斑块进展。
