Skin–Heart Connection

The importance of desmosomes in the human heart is evidenced by arrhythmogenic cardiomyopathy (AC), an inherited disease in which mutations in desmosomal proteins can lead to fatal ventricular arrhythmias and sudden death. The disease is pathologically characterized by right, left-, or biventricular cardiomyopathy with progressive replacement of myocardium with fatty and fibrous tissue and mainly transmitted as an autosomal dominant inheritance pattern.1 A similar cardiac phenotype is found in recessive cardiocutaneous disorders called Naxos disease and Carvajal syndrome, where AC is combined with palmoplantar keratoderma and woolly hair.2 The common structures affected in those diseases are desmosomes, membrane-bound adhesive junctions that are abundantly expressed in the myocardium and stratified epithelia where they maintain tissue integrity under high mechanical forces. Desmosomes consist of Ca2+-dependent adhesion molecules of the cadherin family, which span the extracellular space to connect adjacent cells, and linker proteins of the plakin and catenin families, which form intracellular assemblies linking the desmosomal cadherins to intermediate filaments of the cytoskeleton.3Article see p 230Mechanistic insights of desmosomal function in health and disease have been gathered from experiments either in epithelial cell lines or other artificial expression systems and transgenic mice. Human primary keratinocyte cultures derived from patients via skin biopsies, an easy and less invasive approach, might be an alternative and more personalized approach for mechanistic studies with focus not only on skin diseases but also on the heart because keratinocytes also express all isoforms of cardiac desmosomal proteins.3Because the heart is difficult to access, there are obviously major limitations for studying patient-specific cardiac expression patterns of desmosomal proteins in the tissue of interest. Tissue is usually only available postmortem, associated with a questionable quality …