Abstract: Background: Fabry disease (FD) can present with manifestations limited to the heart. FD cardiomyopathy is characterized by globotriaosylceramide (Gb3) deposition in myocytes, and is accompanied by secondary changes such as myocyte hypertrophy and fibrosis, which cause raised coronary vascular resistance and increased myocardial oxygen demand. Adaptation to hypoxia is a well-established factor involved in the pathogenesis of hypertrophic myocardiopathy, being the most notable change in the metabolic profile of hypertrophied hearts an increased reliance on glucose with an overall reduced oxidative metabolism and lactate production. Lactate, transported by monocarboxylate transporters (MCTs), has been implicated as a mechanism in this process. Aims and hypothesis: To investigate if metabolic adaptation to hypoxia could play a role mechanism in the pathogenesis of the myocardial dysfunction in FD patients. In this study we determine the expression levels of MCT1 in erythrocytes from patients with FD and predominant hypertrophic myocardiopathy. Methods and persons: Peripheral blood samples from three related FD patients (mutation p.Phe113Leu; c.337?T?>?C in GLA gene) with different degree of myocardial hypertrophy and normal systolic function. By Quantitative Flow Cytometry (QCFM) we quantified the amount of MCT1 receptors in the membranes of erythrocytes. Results: MCT1 exhibits significantly increased expression in reticulocites of patients with FD and hypertrophic myocardiopathy when compared to controls and those with no myocardial affectation. In our observation, levels of MCT1 expression are not related with the degree of cardiac dysfunction but with myocardial size. Comments: Our observation suggests that oxidative metabolism should be considered and monitored in FD patients. MCT1 expression changes, whereas an adaptative response to hypoxia, it could be a precocious marker of metabolic dysfunction in patients with FD and a reliable marker of response to the treatment.
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