gamma-Glutamyltransferase activity in human atherosclerotic plaques-Biochemical similarities with the circulating enzyme

Background and purpose: 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. Methods and results: 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 GIST activity, one of which comparable with plasma LDL/GGT complexes. Accordingly, precipitation of P-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. Conclusions: The results obtained suggest the presence ill 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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.