Why do some young and fit athletes suddenly die? Especially endurance athletes? This may be due to an abnormal heart conduction defect arising in a disease state called Arrhythmogenic Right Ventricular Dysplasia (ARVD). This probably happens in a few individuals who develop genetic modification through exercise, and the resultant is that there is scarring and fat infiltration in the heart muscle area that lead to cardiac rhythm disturbances. From Medscape Cardiology: "Arrhythmogenic right ventricular dysplasia is a form of cardiomyopathy where fibrous and fatty tissue replaces normal myocardium, primarily in the RV. Disruption of the architecture of cell-cell coupling sets up a milieu favorable for arrhythmia. In Europe and to a certain extent in the US, ARVD is a not-infrequent cause of sudden death in young athletes. What makes this disease especially interesting is its genetics. Mutations in the genes that code for connecting proteins, called desmosomes, are the culprit. These defects are passed down in an autosomal dominant pattern, but the genotype is variably expressed with incomplete penetrance. This means some patients might suffer early ventricular arrhythmia while others with the same genetic material live into old age. In other words, the genotype has many phenotypes. It has been hypothesized that endurance exercise (remember the ARVD-association with athletes) might induce an ARVD-like disease (phenotype) in genetically susceptible individuals. The Study: Researchers from Birmingham, UK and colleagues in Muenster and Aachen, Germany used genetically modified mice to look at the interaction between exercise and heart disease. They knew that many patients with ARVD harbor mutations in the domain of the desmoglein 2 (DSG2) gene. They were able to genetically engineer mice lacking parts of the DSG2 gene. Those mice with two copies of the deletion (homozygous) developed profound ARVD, whereas those mice with one copy (heterozygous) did not manifest disease. The question then was whether heavy physical exercise could provoke a disease state in genotypically susceptible mice. So they made heterozygous mice swim. Training sessions were done six days a week for up to 90 minutes per day. The research team then looked at both structure and electrical findings in the exercised mice and compared the swimming mice with their wild-type littermates. The exercised and genetically susceptible (heterozygous—one copy of mutation) developed dilated RVs and had easily provoked ventricular arrhythmias. There were no such findings in the wild-type littermates. This simple but elegant experiment led the researchers to conclude that endurance training revealed an ARVD-like phenotype in otherwise-healthy and morphologically inconspicuous mice. During the slide presentation they suggested that these data support the idea that endurance training may be dangerous for carriers of mutations in junctional proteins." The original abstract is here: spo.escardio.org/Abstract.aspx?eevtid=62&fp=83
Posted on: Tue, 02 Jul 2013 21:53:22 +0000
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