Re-expression of alpha skeletal actin as a marker for dedifferentiation in cardiac pathologies.
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 (alphaSKA) and a final predominant expression of alpha cardiac actin (alphaCA). Our objective was to detect whether re-expression of alphaSKA occurred during cardiomyocyte dedifferentiation, a phenomenon that has been observed in different pathologies characterized by myocardial dysfunction. Immunohistochemistry of alphaCA, alphaSKA 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 alphaCA and alphaSKA. Up-regulation of alphaSKA was observed in human ventricular cardiomyocytes showing down-regulation of alphaCA and cardiotin. A patchy re-expression pattern of alphaSKA 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 alphaSKA. Comparable alphaSKA 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 alphaSKA 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.
Driesen
Ronald B
RB
Department of Molecular Cell Biology, Maastricht University, Maastricht, The Netherlands.
Verheyen
Fons K
FK
Debie
Wiel
W
Blaauw
Erik
E
Babiker
Fawzi A
FA
Cornelussen
Richard N M
RN
Ausma
Jannie
J
Lenders
Marie-Hélène
MH
Borgers
Marcel
M
Chaponnier
Christine
C
Ramaekers
Frans C S
FC
D000185:Actinin / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001022:Aortic Valve Insufficiency / Q000378:metabolism / Q000473:pathology; D001281:Atrial Fibrillation / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D054337:Cell Dedifferentiation / Q000502:physiology*; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D006003:Glycogen / Q000378:metabolism; D006041:Goats; D006801:Humans; D017682:Myocardial Stunning / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology*; D020033:Protein Isoforms / Q000378:metabolism; D011817:Rabbits; D015854:Up-Regulation / Q000502:physiology
D000199:Actins; D015415:Biomarkers; D020033:Protein Isoforms; C104594:cardiotin; D000185:Actinin; D006003:Glycogen