Premium
γ‐Glutamyltransferase activity in human atherosclerotic plaques: origin, prooxidant effects and potential roles in progression of disease
Author(s) -
Pompella Alfonso,
Paolicchi Aldo,
Franzini Maria,
Passino Claudio,
Emdin Michele
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a17
Subject(s) - pathogenesis , chemistry , lipoprotein , oxidative stress , biochemistry , enzyme , medicine , endocrinology , cholesterol
Serum γ‐glutamyltransferase (GGT) activity has been identified as a predictor of complications of coronary atherosclerosis and stroke. GGT activity can give rise to prooxidant molecular species, and promotes LDL oxidation in vitro. As oxidative processes are involved at various levels in atherogenesis, and human atherosclerotic lesions do contain variable levels of active GGT, it is conceivable that the enzyme can directly contribute to pathogenesis and progression of atherosclerosis. The biochemical characteristics of GGT protein were compared in plaque tissue (endoarteriectomy) and in serum and platelets obtained from healthy donors and cardiovascular patients. Electrostatic charge of GGT, its association with serum macromolecules, and the molecular weight of its large subunit were analyzed. Both in serum and plaque extracts, two distinct GGT complexes with lipoproteins were found, corresponding to the m.w. of HDL and VLDL/LDL. Further analysis showed the expression in plaques of GGT‐I gene, coding for the complete and active enzyme, as well as its product cysteinyl‐glycine, both in free and protein bound forms. Our observations suggest that the predictive value of serum GGT for cardiovascular death is due to a direct contribution of serum GGT to GGT activity within the plaque, and to prooxidant GGT‐driven reactions. Supported by Italian Ministry for University and Research, FIRB and PRIN Funds.