The genetic landscape of cardiomyopathies

Insights into genetic causes of cardiomyopathies have tremendously contributed to the understanding of the molecular basis and pathophysiology of hypertrophic, dilated, arrhythmogenic, restrictive and left ventricular noncompaction cardiomyopathy. More than thousand mutations in approximately 100 genes encoding proteins involved in many different subcellular systems have been identified indicating the diversity of pathways contributing to pathological cardiac remodeling. Moreover, the classical view based on morphology and physiology has been shifted toward genetic and molecular patterns defining the etiology of cardiomyopathies. Today, novel high-throughput genetic technologies provide an opportunity to diagnose individuals based on their genetic findings, sometimes before clinical signs of the disease occur. However, the challenge remains that rapid research developments and the complexity of genetic information are getting introduced into the clinical practice, which requires dedicated guidance in genetic counselling and interpretation of genetic test results for the management of families with inherited cardiomyopathies

Therapeutic strategies targeting connexins

The connexin family of channel-forming proteins is present in every tissue type in the human anatomy. Connexins are best known for forming clustered intercellular channels, structurally known as gap junctions, where they serve to exchange members of the metabolome between adjacent cells. In their single-membrane hemichannel form, connexins can act as conduits for the passage of small molecules in autocrine and paracrine signalling. Here, we review the roles of connexins in health and disease, focusing on the potential of connexins as therapeutic targets in acquired and inherited diseases as well as wound repair, while highlighting the associated clinical challenges