Aortic valve disease and gamma-glutamyltransferase: accumulation in tissue and relationships with calcific degeneration

Abstract

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.