Cardiomyopathy

Besides platelets, vascular smooth muscle and endothelial cells, VASP is expressed in the human heart (Markert et al. 1996). Both VASP and Mena are expressed in mouse heart, where they are associated with intercalated discs of cardiomyocytes (Gambaryan et al. 2001). Intercalated discs are complex membrane structures separating adjacent cardiomyocytes. Their intracellular side is characterised by a highly organised cytoskeleton rich in N-cadherin, catenins, vinculin and connexins. The displacement of VASP and Mena from cardiac intercalated discs via heart-targeted expression of EVH1 domain in transgenic mice resulted in the disorganisation of intercalated discs (Eigenthaler et al. 2003). The severe consequences of this histological abnormality were myocyte hypertrophy, cardiac dilatation and bradycardia, which led to early postnatal mortality. Mena and VASP were also shown to co-localise in vivo and interact in vitro with Xin, the protein encoded by the human gene 'cardiomyopathy-associated 1' or CMYA1 (van der Ven et al. 2006), and migfilin, a protein that serves the dual function of structural cytoskeletal organiser and transcriptional regulator in cardiomyocytes (Wu 2005). In summary, the scaffolding activity of Ena/VASP proteins seems to be crucial for the correct organisation of the cytoskeleton underlying regions of physical and functional contact between cardiomyocytes. Their important role in the establishment and maintenance of the structural integrity of cardiomyocytes and myocardium makes Ena/VASP proteins interesting candidates for cardiac diseases, in particular congenital cardiomyopathies associated with developmental defects and hypertrophy.

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