| Summary: |
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by deficient alfa-galactosidase A activity that leads to the accumulation of globotriasylceramide (Gb3) in affected tissues, including the heart. Following the introduction of enzyme replacement therapy, early diagnosis and treatment have become essential to slow disease progression and prevent major cardiac complications. In addition to Gb3 accumulation, other mechanisms contribute to the development of Fabry cardiomyopathy. As a slowly progressive form of hypertrophic cardiomyopathy (HCM), Anderson-Fabry disease (FD) resembles the phenotype of the most common sarcomeric forms, although the particular pathophysiology determines distinct clinical presentation and long-term progression. Progress in imaging techniques has improved the diagnosis and staging of FD-related cardiac disease. Myocardial hypertrophy, inflammation and fibrosis can all contribute to disease progression and can be inferred by noninvasive imaging approaches, namely echocardiography, cardiac magnetic resonance, or positron emission tomography. However, a better correlation of imaging data with ongoing myocardial pathophysiological processes is of particular importance for a deeper comprehension of FD cardiomyopathy, for the development of new diagnostic and prognostic disease biomarkers and also for the expansion of alternative or complementary therapies, especially in advanced cardiac FD, where the response to enzyme replacement therapy is poor, with no data suggesting any effect on myocardial fibrosis and inconsistent effects on left ventricular hypertrophy progression.
In this work, we intend to deepen the knowledge of the signalling pathways involved in cardiac remodelling of human FD by comparing the proteomics data from FD myocardial biopsies with normal tissue of heart donor biopsy samples. In this project, we also intend to characterize the process of cardiac remodelling by analyzing the profile of microRNAs related  |
Summary
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by deficient alfa-galactosidase A activity that leads to the accumulation of globotriasylceramide (Gb3) in affected tissues, including the heart. Following the introduction of enzyme replacement therapy, early diagnosis and treatment have become essential to slow disease progression and prevent major cardiac complications. In addition to Gb3 accumulation, other mechanisms contribute to the development of Fabry cardiomyopathy. As a slowly progressive form of hypertrophic cardiomyopathy (HCM), Anderson-Fabry disease (FD) resembles the phenotype of the most common sarcomeric forms, although the particular pathophysiology determines distinct clinical presentation and long-term progression. Progress in imaging techniques has improved the diagnosis and staging of FD-related cardiac disease. Myocardial hypertrophy, inflammation and fibrosis can all contribute to disease progression and can be inferred by noninvasive imaging approaches, namely echocardiography, cardiac magnetic resonance, or positron emission tomography. However, a better correlation of imaging data with ongoing myocardial pathophysiological processes is of particular importance for a deeper comprehension of FD cardiomyopathy, for the development of new diagnostic and prognostic disease biomarkers and also for the expansion of alternative or complementary therapies, especially in advanced cardiac FD, where the response to enzyme replacement therapy is poor, with no data suggesting any effect on myocardial fibrosis and inconsistent effects on left ventricular hypertrophy progression.
In this work, we intend to deepen the knowledge of the signalling pathways involved in cardiac remodelling of human FD by comparing the proteomics data from FD myocardial biopsies with normal tissue of heart donor biopsy samples. In this project, we also intend to characterize the process of cardiac remodelling by analyzing the profile of microRNAs related to hypertrophic cardiomyopathy and their diagnostic and prognostic value.MicroRNAs (miRNAs) are noncoding RNA molecules that play crucial roles in the
pathological process of cardiac remodelling. Accordingly, miRNAs related to FD may represent potential novel diagnostic and therapeutic targets. Results are expected to allow, for the first time, the identification of microRNA signatures in FD that may serve simultaneously as biomarkers and therapeutic targets. Additionally, we intend to characterize the process of myocardial fibrosis using a new molecular imaging technic, determining its value in the diagnosis and prognosis of FD. |