Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a not so rare “disease of the desmosome” with multiple clinical presentations

Biophysics of Titin in Cardiac Health and Disease

“…Endurance athletes have been implicated as having a high risk to develop AC, and it is speculated that this is because endurance sports are associated with long-lasting volume overload of the right ventricle [31]. For these reasons, I decided to subject 10 month old male mice to a five week treadmill exercise regimen to try to instigate expression of the disease phenotype.…”

“…They are looking at the protein levels of desmosomal proteins because AC has been causally linked to various desmosomal mutations [31].…”

“…[42]. To try to instigate development of the disease phenotype we subjected nine month old male mice to five weeks of treadmill exercise, as the increased pre-load associated with sustained exercise has been suggested to explain the reason that endurance athletes have a high risk to develop AC [31]. It has previously been shown that endurance training accelerates the disease phenotype in an AC mouse model deficient in the desmosomal protein plakoglobin [43].…”

“…Mutations in titin have been associated with dilated cardiomyopathy [36], but recently a mutation in titin was linked with arrhythmogenic cardiomyopathy (AC) for the first time [37]. AC has been termed a "disease of the desmosome" because numerous desmosomal mutations have been identified that cause the disease phenotype [31]. The primary phenotype is identified by replacement of the myocardium with fibrofatty tissue, which leads to problems with electrical conduction and arrhythmias early on and reduced contractility and heart failure as patients age.…”

Geographical distribution of plakophilin-2 mutation prevalence in patients with arrhythmogenic cardiomyopathy

“…Arrhythmogenic cardiomyopathy (AC), previously known as arrhythmogenic right ventricular cardiomyopathy or dysplasia (ARVC/D), is a myocardial disease usually with autosomal dominant inheritance and an estimated prevalence of 1:2000 to 1:5000 in the Western world [1,2]. Based on clinical symptomology, the disease affects men more commonly than women (3:1) and usually becomes manifest between the second and the fourth decade of life.…”