Re-expression of Alpha Skeletal Actin As a Marker for Dedifferentiation in Cardiac Pathologies

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2009 Jun 23

PMID 19538254

Citations 25

Authors

Ronald B Driesen

Fons K Verheyen

Wiel Debie

Erik Blaauw

Fawzi A Babiker

Richard N M Cornelussen

Jannie Ausma

Marie-Helene Lenders

Marcel Borgers

Christine Chaponnier

Frans C S Ramaekers

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Loss of Myofibrils in Cardiomyocytes as a Morphological Indicator of Reduced Compensatory Capabilities of Hypertrophied Myocardium.

Sukhacheva T, Serov R, Bockeria L Bull Exp Biol Med. 2024; 178(1):130-138.

PMID: 39579295 DOI: 10.1007/s10517-024-06295-6.

Cardiac maturation.

Sakamoto T, Kelly D J Mol Cell Cardiol. 2023; 187:38-50.

PMID: 38160640 PMC: 10923079. DOI: 10.1016/j.yjmcc.2023.12.008.

Brain Natriuretic Peptide Protects Cardiomyocytes from Apoptosis and Stimulates Their Cell Cycle Re-Entry in Mouse Infarcted Hearts.

Bon-Mathier A, Deglise T, Rignault-Clerc S, Bielmann C, Mazzolai L, Rosenblatt-Velin N Cells. 2023; 12(1).

PMID: 36611800 PMC: 9818267. DOI: 10.3390/cells12010007.

The Role of Lamins in the Nucleoplasmic Reticulum, a Pleiomorphic Organelle That Enhances Nucleo-Cytoplasmic Interplay.

Stiekema M, Houben F, Verheyen F, Borgers M, Menzel J, Meschkat M Front Cell Dev Biol. 2022; 10:914286.

PMID: 35784476 PMC: 9243388. DOI: 10.3389/fcell.2022.914286.

The Role of Oncostatin M and Its Receptor Complexes in Cardiomyocyte Protection, Regeneration, and Failure.

Kubin T, Gajawada P, Bramlage P, Hein S, Berge B, Cetinkaya A Int J Mol Sci. 2022; 23(3).

PMID: 35163735 PMC: 8836542. DOI: 10.3390/ijms23031811.

References

Ausma J, Cleutjens J, Thone F, Flameng W, Ramaekers F, Borgers M . Chronic hibernating myocardium: interstitial changes. Mol Cell Biochem. 1995; 147(1-2):35-42. DOI: 10.1007/BF00944781. View

Suurmeijer A, Clement S, Francesconi A, Bocchi L, Angelini A, Van Veldhuisen D . Alpha-actin isoform distribution in normal and failing human heart: a morphological, morphometric, and biochemical study. J Pathol. 2003; 199(3):387-97. DOI: 10.1002/path.1311. View

Sharov V, Sabbah H, Ali A, Shimoyama H, Lesch M, Goldstein S . Abnormalities of cardiocytes in regions bordering fibrous scars of dogs with heart failure. Int J Cardiol. 1997; 60(3):273-9. DOI: 10.1016/s0167-5273(97)00117-4. View

Winegrad S, Wisnewsky C, Schwartz K . Effect of thyroid hormone on the accumulation of mRNA for skeletal and cardiac alpha-actin in hearts from normal and hypophysectomized rats. Proc Natl Acad Sci U S A. 1990; 87(7):2456-60. PMC: 53708. DOI: 10.1073/pnas.87.7.2456. View

Ruzicka D, Schwartz R . Sequential activation of alpha-actin genes during avian cardiogenesis: vascular smooth muscle alpha-actin gene transcripts mark the onset of cardiomyocyte differentiation. J Cell Biol. 1988; 107(6 Pt 2):2575-86. PMC: 2115638. DOI: 10.1083/jcb.107.6.2575. View

Eppenberger-Eberhardt M, Flamme I, Kurer V, Eppenberger H . Reexpression of alpha-smooth muscle actin isoform in cultured adult rat cardiomyocytes. Dev Biol. 1990; 139(2):269-78. DOI: 10.1016/0012-1606(90)90296-u. View

Dlugosz A, Antin P, Nachmias V, Holtzer H . The relationship between stress fiber-like structures and nascent myofibrils in cultured cardiac myocytes. J Cell Biol. 1984; 99(6):2268-78. PMC: 2113583. DOI: 10.1083/jcb.99.6.2268. View

Rhee D, Sanger J, Sanger J . The premyofibril: evidence for its role in myofibrillogenesis. Cell Motil Cytoskeleton. 1994; 28(1):1-24. DOI: 10.1002/cm.970280102. View

Vermeulen J, McGuire M, Opthof T, Coronel R, de Bakker J, Klopping C . Triggered activity and automaticity in ventricular trabeculae of failing human and rabbit hearts. Cardiovasc Res. 1994; 28(10):1547-54. DOI: 10.1093/cvr/28.10.1547. View

10.

Dispersyn G, Geuens E, Ver Donck L, Ramaekers F, Borgers M . Adult rabbit cardiomyocytes undergo hibernation-like dedifferentiation when co-cultured with cardiac fibroblasts. Cardiovasc Res. 2001; 51(2):230-40. DOI: 10.1016/s0008-6363(01)00326-1. View

11.

Maes A, Flameng W, Nuyts J, Borgers M, Shivalkar B, Ausma J . Histological alterations in chronically hypoperfused myocardium. Correlation with PET findings. Circulation. 1994; 90(2):735-45. DOI: 10.1161/01.cir.90.2.735. View

12.

Driesen R, Verheyen F, Dispersyn G, Thone F, Lenders M, Ramaekers F . Structural adaptation in adult rabbit ventricular myocytes: influence of dynamic physical interaction with fibroblasts. Cell Biochem Biophys. 2006; 44(1):119-28. DOI: 10.1385/CBB:44:1:119. View

13.

Thijssen V, Borgers M, Lenders M, Ramaekers F, Suzuki G, Palka B . Temporal and spatial variations in structural protein expression during the progression from stunned to hibernating myocardium. Circulation. 2004; 110(21):3313-21. DOI: 10.1161/01.CIR.0000147826.13480.99. View

14.

Ausma J, van der Velden H, Lenders M, van Ankeren E, Jongsma H, Ramaekers F . Reverse structural and gap-junctional remodeling after prolonged atrial fibrillation in the goat. Circulation. 2003; 107(15):2051-8. DOI: 10.1161/01.CIR.0000062689.04037.3F. View

15.

Dabiri G, Turnacioglu K, Sanger J, Sanger J . Myofibrillogenesis visualized in living embryonic cardiomyocytes. Proc Natl Acad Sci U S A. 1997; 94(17):9493-8. PMC: 23235. DOI: 10.1073/pnas.94.17.9493. View

16.

Svitkina T, Neyfakh Jr A, Bershadsky A . Actin cytoskeleton of spread fibroblasts appears to assemble at the cell edges. J Cell Sci. 1986; 82:235-48. DOI: 10.1242/jcs.82.1.235. View

17.

Komuro I, Katoh Y, Kaida T, Shibazaki Y, Kurabayashi M, Hoh E . Mechanical loading stimulates cell hypertrophy and specific gene expression in cultured rat cardiac myocytes. Possible role of protein kinase C activation. J Biol Chem. 1991; 266(2):1265-8. View

18.

Corradi D, Callegari S, Benussi S, Maestri R, Pastori P, Nascimbene S . Myocyte changes and their left atrial distribution in patients with chronic atrial fibrillation related to mitral valve disease. Hum Pathol. 2005; 36(10):1080-9. DOI: 10.1016/j.humpath.2005.07.018. View

19.

Eppenberger M, Hauser I, Baechi T, Schaub M, Brunner U, Dechesne C . Immunocytochemical analysis of the regeneration of myofibrils in long-term cultures of adult cardiomyocytes of the rat. Dev Biol. 1988; 130(1):1-15. DOI: 10.1016/0012-1606(88)90408-3. View

20.

Dispersyn G, Ausma J, Thone F, Flameng W, Vanoverschelde J, Allessie M . Cardiomyocyte remodelling during myocardial hibernation and atrial fibrillation: prelude to apoptosis. Cardiovasc Res. 2000; 43(4):947-57. DOI: 10.1016/s0008-6363(99)00096-6. View