Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiomyopathy associated with cardiac arrhythmias originating in the right ventricle, heart failure, and sudden cardiac death. Development of ARVD/C type 1 has been attributed to differential expression of transforming growth factor beta 3 (TGFβ3). Several mechanisms underlying the molecular basis of ARVD/C type 1 have been proposed. Evaluating previously described mechanisms might elucidate how TGFβ3 contributes to disease progression in ARVD/C type 1. Here we review how TGFβ3 can induce fibrogenesis through Smad and/or β-catenin signaling. Moreover, the role of apoptosis is addressed. Finally the extent to which the immune system has been demonstrated to be a modulating and amplifying agent in the onset and progression of ARVD/C in general is discussed. 1. Introduction Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), also known as ARVD, ARVC, and ARVC/D, is an inherited cardiomyopathy. It is associated with cardiac arrhythmias originating in the right ventricle, heart failure, and sudden cardiac death [1]. Demanding physical activity is a significant risk factor for the development of ARVD/C. The estimated prevalence of ARVD/C varies between 1 in 2,000 and 1 in 5,000 [2, 3], but a higher prevalence has also been suggested [4, 5]. A higher prevalence of ARVD/C in male is a consistent finding, with an approximate ratio of 3？:？1 according to review papers [1, 2]. The actual ratio is, however, highly variable [6–11]. Most forms of ARVD/C are inherited in an autosomal dominant manner. Only two forms, that is, Naxos disease and Carvajal syndrome [12], are autosomal recessive diseases. Even though most forms of ARVD/C are autosomal dominant, disease penetrance is often incomplete and variable expression is observed, even among members of the same family [13]. This variability is poorly understood, and it significantly complicates genetic counseling [14]. To help establish a diagnosis, Task Force Criteria have been proposed by McKenna et al. [15] and revised by Marcus et al. [16] to assure diagnostic sensitivity and specificity. Not all criteria must be fulfilled to recognize the disease as ARVD/C. A first criterion is global and/or regional structural alterations and cardiac dysfunction, which is manifested as a reduction of the right ventricular ejection fraction. The disintegration of the cardiac wall is characterized by gradual fibrofatty replacement in the myocardium [17, 18], as illustrated in Figure 1. The progressive thinning of the ventricular wall
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