Content area

Full text

Alena Jirásková [1] and Giulia Bortolussi [1] and Gabriela Dostálová [2] and Lenka Eremiášová [2] and Lubor Golaň [2] and Vilém Danzig [2] and Aleš Linhart [2] and Libor Vítek [1; 3]

Academic Editor: Ryuichi Morishita

1, Department of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Katerinska 32, 12000 Prague 2, Czech Republic, cuni.cz

2, 2nd Department of Internal Medicine and Department of Cardiovascular Medicine, 1st Faculty of Medicine, Charles University, Katerinska 32, 12000 Prague 2, Czech Republic, cuni.cz

3, 4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University, Katerinska 32, 12000 Prague 2, Czech Republic, cuni.cz

Received May 22, 2017; Accepted Jul 9, 2017

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

1. Introduction

Fabry disease (FD, OMIM 301500), an X-linked metabolic disorder, is caused by a deficiency of the lysosomal enzyme α-galactosidase A, resulting in the accumulation of glycosphingolipids (in particular globotriaosylceramide (GB3)) in endothelial cells and other tissues [1, 2]. The majority of FD complications results from progressive damage to the central and peripheral nervous system, kidney, and heart due to severe vasculopathy [2, 3]. Indeed, α-galactosidase A deficiency was shown to accelerate atherosclerosis in apolipoprotein E-deficient mice [4]. Moreover, endothelial dysfunction was also reported in a clinical study on FD patients [5], but the vascular damage in FD differs from classical atherosclerosis [6–8]. The storage in FD, predominantly found in endothelial and smooth muscle cells as well as in stenotic lesions, is characterized by intimal and subintimal proliferation [6]. Increasing clinical evidence suggest that FD is a rather heterogeneous disease differing in the age of manifestation, severity, and organ involvement depending on specific genetic background [9]. There is also an increasing evidence that FD prevalence may be largely underestimated [9, 10], which strongly supports the importance of known and reasons for additional putative genetic factors influencing its clinical manifestation.

The pathological processes in FD are associated with increased oxidative, nitrosative, and carbonyl stress as evidenced by excessive production of reactive oxygen species (ROS) [11–13]; increased plasma and urinary carbonylated proteins [14]; and nitrotyrosine in plasma, cardiac, and vascular tissues [15–17], resulting...

Show less