Prognostic Value and Determinants of a Hypointense Core in T2-Weighted Cardiac Magnetic Resonance in Acute Reperfused St-Elevation Myocardial Infarction

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disorder characterized by fibro-fatty replacement of cardiomyocytes. The cardinal manifestations are arrhythmias, sudden cardiac death, and seldom heart failure. Mutations in genes encoding desmosomal proteins and their interaction partners have been implicated in the pathogenesis of ARVC and it is now widely accepted that ARVC is a disease caused by abnormal cell–cell adhesion. The mechanism(s) by which mutations in desmosomal proteins lead to fibro-fatty replacement remains to be fully elucidated. To this aim over the last 10 years different transgenic and targeted mouse models have been developed, these models and what they have taught us will be discussed in this review.

Section: Discussionmentioning

confidence: 99%

“…All observed changes were exacerbated and expedited when mice were subjected to exercise training (model Pg3; Kirchhof et al, 2006). Load reducing therapy is able to prevent these symptoms of ARVC in Pg ± mice (model Pg4; Fabritz et al, 2011). …”

Section: Plakoglobin Targeted Deletion and Overexpression Modelsmentioning

confidence: 99%

Mouse Models in Arrhythmogenic Right Ventricular Cardiomyopathy

Lodder¹,

Rizzo²

2012

“…Consistent with the concept of mechanical overload of the cell–cell junctions, the development of cardiomyopathy in mouse models can be influenced by altering the mechanical load on the heart: endurance training accelerates (Kirchhof et al, 2006) and pharmacological therapy that lowers the hemodynamic load slows the development of the ARVC phenotype in heterozygous plakoglobin deficient mice (Fabritz et al, 2011). Indeed, ARVC patients engaged in endurance training appear to have a more severe ARVC phenotype than those that are not (Sen-Chowdhry et al, 2007b).…”

Section: Arrhythmogenic Right Ventricular Cardiomyopathymentioning

confidence: 94%

Diagnostic Dilemmas: Overlapping Features of Brugada Syndrome and Arrhythmogenic Right Ventricular Cardiomyopathy

Hoogendijk¹

2012

Arrhythmogenic right ventricular cardiomyopathy (ARVC) and Brugada syndrome are distinct clinical entities which diagnostic criteria exclude their coexistence in individual patients. ARVC is a myocardial disorder characterized by fibro-fatty replacement of the myocardium and ventricular arrhythmias. In contrast, the Brugada syndrome has long been considered a functional cardiac disorder: no gross structural abnormalities can be identified in the majority of patients and its electrocardiographic hallmark of coved-type ST-segment elevation in right precordial leads is dynamic. Nonetheless, a remarkable overlap in clinical features has been demonstrated between these conditions. This review focuses on this overlap and discusses its potential causes and consequences.

“…Overexpression of mutant desmosomal genes or introduction of mutant desmosomal genes in mice (Pilichou et al, 2009) and other animal model systems (zebrafish) will help further to understand ARVC/D disease development and treatment (Macrae, 2010; Fabritz et al, 2011). …”

Section: Effects Of Mutations In Genes Encoding For Cardiomyocyte Adhmentioning

confidence: 99%

Gene Mutations Resulting in the Development of ARVC/D Could Affect Cells of the Cardiac Conduction System

Pieperhoff¹

2012

In contrast to epithelial cells, cardiomyocytes are connected by complex hybrid-type adhering junctions, termed composite junctions (areae compositae). Composite junctions are found to be composed of typical desmosomal as well as adherens junction proteins. Therefore, in adult mammalian cardiomyocytes desmosomal proteins are not restricted to the relatively small desmosomes but are indirectly involved in anchoring the myofibrillar actin filaments. Subsequent investigations revealed that the formation of composite junctions is a rather late event during mammalian heart development and vertebrate heart evolution. Nascent, more round shaped cardiomyocytes of early developmental stages are connected by desmosomes and separate adherens junctions quite similar to cells of epithelial origin. During progression of development both types of adhering junctions seem to gradually fuse at the two poles of the mature mammalian cardiomyocytes to establish the hybrid-type composite junctions. Recently, we demonstrated that the specialized cardiomyocytes of the cardiac conduction system exhibit high amounts of desmosomes, not fully established composite junctions and adherens junctions. This underlines the fact that cells of the cardiac conduction system are known to resemble cardiomyocytes in their nascent state and do not undergo working myocardial differentiation. However, the astonishing high amount of desmosomal protein containing adhering junctions connecting, e.g., Purkinje fibers raises the possibility that pacemaker and conductive tissue may be affected by desmosomal gene mutations in ARVC/D patients.