Sp021cardiovascular-renal Remodeling in Fabry Disease: Possible Involvement of Oxidative Stress. a Molecular Biology Approach
Year: 2018
Type: conference-abstract
Abstract: INTRODUCTION AND AIMS: Fabry disease (FD) is an X-linked rare disease characterized by deficient expression and activity of α-galA and consequent lysosomal accumulation of its substrates in various organs. Notwithstanding the enzyme replacement therapy (ERT), FD is a progressive disease with serious cardiovascular-renal implications such as myocardial infarction, stroke and kidney failure. It has recently been shown that Gb3 accumulation induces oxidative stress (OxSt) by increasing proinflammatory cytokine and reducing nitric oxide production. METHODS: As OxSt has a primary role in the induction of cardiovascular-renal remodeling, we aimed to evaluate the state of OxSt in 10 FD in terms of protein expression p22phox, subunit of NADH/NADPH oxidase essential for the production of superoxide; phosphorylation of MYPT-1, marker of Rho kinase activation, deeply involved in OxSt signaling for the induction of cardiovascular-renal remodeling; phosphorylation of Extracellular Signal Regulated Kinase 1/2 (ERK1/2), essential regulator of the cardiovascular hypertrophy; protein expression of Heme oxygenase (HO)-1, protective from OxSt and antiinflammatory and finally the left ventricular mass in FD patients. RESULTS: Compared to healthy subjects, p22phox was significantly higher in FD (1.04±0.12 d.u. vs 0.48±0.05 d.u. p=0.01), as well as the phosphorylation of MYPT-1 (1.79±0.23 vs 1.06±0.13, p<0.05). Phosphorylation of ERK1/2 was significantly reduced in FD (0.91±0.08 vs 1.53±0.17, p=0.004) as was the protein expression of HO-1 (8.57±1.03 vs 14.03±1.60, p=0.02). Cardiac left ventricular mass was higher in both males (123.72 g/m2 ) and females (112.88 g/m2), compared to normal values according to guidelines. CONCLUSIONS: This study demonstrates that OxSt is activated in FD and could contribute to cardiovascular-renal remodeling through Rho kinase signaling. Therefore the inhibition of OxSt by either pharmacological or nutritional measure might be a useful additional intervention for the prevention/treatment of cardiovascular-renal remodeling.
Institution: University of Padua
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2803326490