The potential roles of gamma-glutamyltransferase activity in the progression of atherosclerosis and cardiovascular diseases.

The oxidation of low density lipoproteins (LDL) is regarded as a critical factor in the pathogenesis of atherosclerosis, especially the initial steps of the disease. In addition, other oxidative events have been shown to participate in the progression of atherosclerosis and precipitation of cardiovascular events, through modulation of important components of lesions of the vessel wall (smooth muscle cell proliferation, protease/antiprotease balance, endothelial functions). Our recent studies have provided evidence that the enzyme gamma-glutamyltransferase (GGT), normally found in serum, is often accumulated within the plaque environment in substantial amounts, and that this activity is a potential source of a variety of prooxidant species. Concurrently, epidemiological research has conclusively documented that the serum levels of GGT are an independent factor in prognosis of myocardial infarction and stroke in atherosclerotic patients. Several signs suggest that the GGT appearing in plaque tissue may originate from the serum enzyme, which in facts associates with the circulating lipoprotein fractions. Thus, data seem to point out that pathogenesis of atherosclerosis – and in particular of the events leading to progression of the disease and acute cardiovascular events – might include an as yet unexplored pathway, based on the prooxidant effects of gamma-glutamyltransferase accumulating as a result of LDL entry in the vessel wall.