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Cardiomyocyte architecture in development and disease

Basic Sciences, Pharmacology, Genomics and Cardiovascular Pathology

The complex structure of the heart is generated during cardiac development. In this session,the mechanisms of how the myocardium generates its three-dimensional structure during embryonic development were presented. Moreover the complex histology of the adult ventricle and the alterations in cardiac disease were discussed.

Deborah Henderson (Newcastle-upon-Tyne, UK) gave the first presentation on the Planar Cell Polarity (PCP) pathway in ventricular wall formation in the mouse embryo. The PCP pathway is highly conserved during evolution and is involved in generating polarity, and thus, making the front of the cell different from its back. Mouse mutants lacking genes involved in PCP signalling such as Vangl2 or Scrib display severe defects in heart development. Defective PCP signalling results in a non-polarized distribution of adhesion molecules such as N-cadherin and very recent data in zebrafish hearts suggest that the PCP pathway is also involved in controlling membrane localization of ion channels and pumps.

Henderson also discussed experiments involving the downstream effectors of the PCP pathway, which is the Rho/Rac/Cdc42 family of small GTPases. Knockdown of these genes in cardiac mycoytes strongly affected the structure of cardiac myocytes. An important challenge in the future will be to learn how the PCP pathway gets activated and modulated during cardiac development and whether PCP signalling could be involved in cardiac disease.

The second presentation was by Sigoleine Meilhac from the laboratory of Margret Buckingham (Pasteur Institute, Paris). Meilhac reported on her clone marking experiments using the nLaacZ technology in mice, which established that during early development two clonally distinct populations make up the heart. The first clone generates the left ventricle, while the second population is mainly involved in generating the tissues of the right ventricle and outflow tract and also part of the inflow tracts. These clones can be followed during later development suggesting that some of these display specific growth patterns, which depends on their location. Potentially their growth pattern is affected by the PCP pathway. Another topic on which this group is currently active is to find out how clonal growth controls cardiac looping morphogenesis.

Paul Lukenheimer (University of Muenster, Germany) presented his work on the structure of the myocardial wall in the adult left ventricle. It is well known that the myocardial wall has a complex structure. Myocytes are built up in tissue strands which have a specific orientation being circumferentially organized in the middle layer, while myocytes are orientated in a spiral form of opposite direction in the epicardial and endocardial layers. This tissue layering is important for proper force development and myocardial relaxation. A challenge for the future will be to define the pathways that establish this complex histology during myocardial development.

The last presentation of this session was by Annalisa Angelini (University of Padova, Italy). She presented examples of how myocardial disease affects the cardiac architecture and histology of the ventricular myocardium. Dr. Angelini presented examples of the tissue structure in hypertrophic, dilated and noncompaction cardiomyopathy. Interestingly,the current knowledge of the underlying genetics suggests that the same mutation in a gene encoding a myofibrillar protein such as actin, or myosin heavy chain can result in a spectrum of cardiomyopathies. This may be due to modifier genes, which modulate the effects of a particular mutation, or alternatively, the tissue has different options to respond to the underlying dysfunction.




Cardiomyocyte architecture in development and disease

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.