The differences between both forms of EDMD in the level of antibodies at diagnosis and at follow-up is hard to explain. They are possibly related to the fact that, in AD-EDMD, damage of the left ventricle muscle cells predominates and is increasing with disease progression, in the X-EDMD, mainly disturbances in heart conductivity are present. In X-EDMD, autoimmunity gradually subsides, which is also observed in some autoimmune disorders such as insulin dependent Inhibitors,research,lifescience,medical diabetes type 1 (28). This is
not the case in AD-EDMD. Whatever the role of anti-heart antibodies, their level in the blood might be a useful non-invasive marker in Inhibitors,research,lifescience,medical predicting the susceptibility of the EDMD patients at risk of developing DCM, especially as it often causes sudden death of the patients even with no evident
preceding cardiac symptoms. Acknowledgments The study was conducted after approval (No KB 2/2005) of the ethics committee for human research at the Medical University of Warsaw. The study was supported by a grant from the State Committee for Scientific Research (No 2PO5B 106 29) to Prof. Irena Hausmanowa-Petrusewicz).
Many mutations in caveolin-3 gene have been detected in autosomal Inhibitors,research,lifescience,medical dominant limb-girdle muscular dystrophy (LGMD) 1C and autosomal dominant rippling muscle disease (AD-RMD) (8, 9). Mutations of the caveolin-3 gene cause a significant reduction in the cell surface level of caveolin-3 protein in a dominant-negative fashion and, to a lesser
extent, selleck chemicals mistargeting of the mutant caveolin-3 protein Inhibitors,research,lifescience,medical to the Golgi complex (8–10). The loss of caveolin-3 by mutations of the caveolin-3 Inhibitors,research,lifescience,medical gene in LGMD1C/AD-RMD patients has resulted in subsequent abnormalities of caveolin-3-binding molecules. The enzymatic activity of neuronal nitric oxide synthase, which is strongly suppressed by caveolin-3, increases in the skeletal muscles from a transgenic mouse model of LGMD1C and LGMD1C/AD-RMD patients (11, 12). Consistently, cytokine-induced NO production increases in C2C12 myoblast cells transfected with LGMD1C/AD-RMD-type mutant caveolin-3 compared to ones transfected with wild-type caveolin-3 (9). Src tyrosine kinase, a membrane tyrosine kinase whose activation Calpain regulates the balance between cell survival and cell death, is extremely activated and accumulates not in the plasma membrane but in the perinuclear region in cells transfected in LGMD1C/AD-RMD mutant caveolin-3 (13). Muscle-specific phosphofruktokinase, an enzyme of central importance in the regulation of glycolytic metabolism is also significantly reduced in cells transfected with LDMD1C/AD-RMD mutant caveolin-3 probably through ubiquitin-proteasomal degradation (14).