Re-expression of alpha skeletal actin as a marker for dedifferentiation in cardiac pathologies
Driesen, Ronald × Verheyen, Fons K Debie, Wiel Blaauw, Erik Babiker, Fawzi A Cornelussen, Richard N. M Ausma, Jannie Lenders, Marie-Helene Borgers, Marcel Chaponnier, Christine Ramaekers, Frans C. S #
Wiley-Blackwell Publishing Ltd.
Journal of Cellular and Molecular Medicine vol:13 issue:5 pages:896-908
Differentiation of foetal cardiomyocytes is accompanied by sequential actin isoform expression, i.e. down-regulation of the 'embryonic' alpha smooth muscle actin, followed by an up-regulation of alpha skeletal actin (alpha SKA) and a final predominant expression of alpha cardiac actin (alpha CA). Our objective was to detect whether re-expression of alpha SKA occurred during cardiomyocyte dedifferentiation, a phenomenon that has been observed in different pathologies characterized by myocardial dysfunction. Immunohistochemistry of alpha CA, alpha SKA and cardiotin was performed on left ventricle biopsies from human patients after coronary bypass surgery. Furthermore, actin isoform expression was investigated in left ventricle samples of rabbit hearts suffering from pressure-and volume-overload and in adult rabbit ventricular cardiomyocytes during dedifferentiation in vitro. Atrial goat samples up to 16 weeks of sustained atrial fibrillation (AF) were studied ultrastructurally and were immunostained for alpha CA and alpha SKA. Up-regulation of alpha SKA was observed in human ventricular cardiomyocytes showing down-regulation of alpha CA and cardiotin. A patchy re-expression pattern of alpha SKA was observed in rabbit left ventricular tissue subjected to pressure-and volume-overload. Dedifferentiating cardiomyocytes in vitro revealed a degradation of the contractile apparatus and local re-expression of alpha SKA. Comparable alpha SKA staining patterns were found in several areas of atrial goat tissue during 16 weeks of AF together with a progressive glycogen accumulation at the same time intervals. The expression of alpha SKA in adult dedifferentiating cardiomyocytes, in combination with PAS-positive glycogen and decreased cardiotin expression, offers an additional tool in the evaluation of myocardial dysfunction and indicates major changes in the contractile properties of these cells.