Partial cell fusion: A newly recognized type of communication between dedifferentiating cardiomyocytes and fibroblasts

Driesen, Ronald B.; Dispersyn, Gerrit D.; Verheyen, Fons; Eijnde, Stefan M. van den; Hofstra, Leo; Thoné, Fred; Dijkstra, Petra; Debie, W. M. H.; Borgers, M.; Ramaekers, Frans C.S.

doi:10.1016/j.cardiores.2005.05.020

Cited by 48 publications

(47 citation statements)

References 37 publications

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“…Furthermore, within the border zone of infarcted myocardium viable vacuolated cells were observed which were surrounded by fibrotic tissue. Co-culturing of adult rabbit CM's with cardiac fibroblasts resulted in typical structural characteristics of CM dedifferentiation, resembling human myocardial hibernation [3,12,13,16]. Such hibernating cardiomyocytes have previously been reported at the borders of micro-infarctions induced in sheep after injection of macro-beads into the LAD or CX coronary artery [5] and in regions bordering fibrous scars of dogs with heart failure [4].…”

Section: Discussionmentioning

confidence: 76%

Structural remodelling of cardiomyocytes in the border zone of infarcted rabbit heart

et al. 2007

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Cardiomyocyte dedifferentiation, as detected in hibernating myocardium of chronic ischemic patients, is one of the characteristics seen at the border of myocardial infarcts in small and large animals. Our objectives were to study in detail the morphological changes occurring at the border zone of a rabbit myocardial infarction and its use as model for hibernating myocardium. Ligation of the left coronary artery (LAD) was performed on rabbit hearts and animals were sacrificed at 2, 4, 8 and 12 weeks postinfarction. These hearts together with a non-infarcted control heart were perfusion-fixed and tissue samples were embedded in epoxy resin. Hibernating cardiomyocytes were mainly distributed in the non-infarcted region adjacent to the border zone of infarcted myocardium but only in a limited number. In the border zone itself vacuolated cardiomyocytes surrounded by fibrotic tissue were frequently observed. Ultrastructural analysis of these vacuolated cells revealed the presence of a basal lamina inside the vacuoles adjacent to the surrounding membrane, the presence of pinocytotic vesicles and an association with cisternae of the sarcoplasmatic reticulum. Myocyte quantitative analyses revealed a gradual increase in vacuolar area/total cell area ratio and in collagen fibril deposition inside the vacuoles from 2 to 12 weeks post-infarction. Related to the remote zone, the increase in cell width of myocytes located in and adjacent to the border zone demonstrated cellular hypertrophy. These results indicate the occurrence of cardiomyocyte remodelling mechanisms in the border zone and adjacent regions of infarcted myocardium. It is suggested that the vacuoles represent plasma membrane invaginations and/or dilatations of T-tubular structures.

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Section: Discussionmentioning

confidence: 76%

Structural remodelling of cardiomyocytes in the border zone of infarcted rabbit heart

et al. 2007

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“…It is believed that viral induced microfusions may be involved in viral spreading. In addition, stable microfusion-like structures have been described between fibroblasts and cardiomyocytes (Driesen et al, 2005). Although in viruscell fusion and intracellular membrane fusion a lot is known about the initial steps leading to fusion pore formation, relatively little is known about fusion pore expansion (Scepek et al, 1998;Dutch and Lamb, 2001;Haller et al, 2001;Gibbons et al, 2004;Jaiswal et al, 2004;Leikina et al, 2004;Nolan et al, 2006).…”

Section: Genes and Kinetic Behavior Characteristic Of Developmental Cmentioning

confidence: 99%

Genetic Control of Fusion Pore Expansion in the Epidermis ofCaenorhabditis elegans

Gattegno

Mittal

Valansi

et al. 2007

MBoC

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Developmental cell fusion is found in germlines, muscles, bones, placentae, and stem cells. In Caenorhabditis elegans 300 somatic cells fuse during development. Although there is extensive information on the early intermediates of viralinduced and intracellular membrane fusion, little is known about late stages in membrane fusion. To dissect the pathway of cell fusion in C. elegans embryos, we use genetic and kinetic analyses using live-confocal and electron microscopy. We simultaneously monitor the rates of multiple cell fusions in developing embryos and find kinetically distinct stages of initiation and completion of membrane fusion in the epidermis. The stages of cell fusion are differentially blocked or retarded in eff-1 and idf-1 mutants. We generate kinetic cell fusion maps for embryos grown at different temperatures. Different sides of the same cell differ in their fusogenicity: the left and right membrane domains are fusion-incompetent, whereas the anterior and posterior membrane domains fuse with autonomous kinetics in embryos. All but one cell pair can initiate the formation of the largest syncytium. The first cell fusion does not trigger a wave of orderly fusions in either direction. Ultrastructural studies show that epidermal syncytiogenesis require eff-1 activities to initiate and expand membrane merger. INTRODUCTIONCell fusion is a ubiquitous and highly controlled process in eukaryotes. Developmental cell fusion is vital for mating and fertilization in yeast and humans, respectively. Cell fusion is required for the formation and maintenance of the muscular-skeletal system in vertebrates, in muscle fibers in Drosophila, and in nearly one third of all cells in Caenorhabditis elegans (Podbilewicz and White, 1994;Heiman and Walter, 2000;Wassarman et al., 2001;Abmayr et al., 2003;Shemer and Podbilewicz, 2003;Chen and Olson, 2005). In C. elegans, diverse cell fusions essential for organ formation and cell fate determination have recently become paradigms for developmental cell fusion (Podbilewicz and White, 1994;Mohler et al., 1998;Nguyen et al., 1999;Sharma-Kishore et al., 1999;Alper and Kenyon, 2002;Mohler et al., 2002;Shemer and Podbilewicz, 2002, 2003;Witze and Rothman, 2002). Cell fusion functions to sculpt organs and to accomplish defined body shapes (Sharma-Kishore et al., 1999;Witze and Rothman, 2002;Shemer and Podbilewicz, 2003). eff-1 (epithelial fusion failure) was identified as a gene encoding type I membrane proteins required for diverse epithelial cell fusion reactions. Mutations in eff-1 result in failure of epithelial cell fusion and developmental defects in organs where cell fusion normally occurs (Mohler et al., 2002;Shemer, 2002;Shemer and Podbilewicz, 2002). The activity of eff-1 is strongly regulated by homeobox containing genes (Shemer and Podbilewicz, 2002, 2003;Cassata et al., 2005). Other transcription and signaling factors have been shown to control the cell fusion process in C. elegans (Nilsson et al., 1998;Ch'ng and Kenyon, 1999;Shemer et al., 2000;Alper and Kenyon, 2001;Chen ...

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“…When plated in primary culture, cardiac fibroblasts form physical interactions with cardiac myocytes through establishment of gap-junctional channels (6,8,14). With the use of a heterocellular culture model, it was established that fibroblasts are capable of relaying electrical excitation over distances as long as 300 m between strands of cardiac myocytes (14).…”

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confidence: 99%

Neonatal rat cardiac fibroblasts express three types of voltage-gated K⁺ channels: regulation of a transient outward current by protein kinase C

Walsh¹,

Zhang²

2008

American Journal of Physiology-Heart and Circulatory Physiology

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Walsh KB, Zhang J. Neonatal rat cardiac fibroblasts express three types of voltage-gated K ϩ channels: regulation of a transient outward current by protein kinase C. Am J Physiol Heart Circ Physiol 294: H1010-H1017, 2008. First published December 21, 2007 doi:10.1152/ajpheart.01195.2007.-Cardiac fibroblasts regulate myocardial development via mechanical, chemical, and electrical interactions with associated cardiomyocytes. The goal of this study was to identify and characterize voltage-gated K ϩ (Kv) channels in neonatal rat ventricular fibroblasts. With the use of the whole cell arrangement of the patch-clamp technique, three types of voltagegated, outward K ϩ currents were measured in the cultured fibroblasts. The majority of cells expressed a transient outward K ϩ current (Ito) that activated at potentials positive to Ϫ40 mV and partially inactivated during depolarizing voltage steps. Ito was inhibited by the antiarrhythmic agent flecainide (100 M) and BaCl2 (1 mM) but was unaffected by 4-aminopyridine (4-AP; 0.5 and 1 mM). A smaller number of cells expressed one of two types of kinetically distinct, delayed-rectifier K ϩ currents [IK fast (IKf) and IK slow (IKs)] that were strongly blocked by 4-AP. Application of phorbol 12-myristate 13-acetate, to stimulate protein kinase C (PKC), inhibited Ito but had no effect on IKf and IKs. Immunoblot analysis revealed the presence of Kv1.4, Kv1.2, Kv1.5, and Kv2.1 ␣-subunits but not Kv4.2 or Kv1.6 ␣-subunits in the fibroblasts. Finally, pretreatment of the cells with 4-AP inhibited angiotensin II-induced intracellular Ca 2ϩ mobilization. Thus neonatal cardiac fibroblasts express at least three different Kv channels that may contribute to electrical/chemical signaling in these cells. cardiac fibroblasts DEVELOPMENT OF THE VERTEBRATE myocardium requires the interaction of several cell types, including myocytes, fibroblasts, smooth muscle cells, and endothelial cells (2, 3). Although cardiac myocytes make up the bulk of the myocardial volume, the cardiac fibroblast is the most numerous cell type found in the heart and functions in the deposition of the extracellular matrix (2, 3). In addition, fibroblasts can serve as "sentinel cells" that coordinate the myocardial response to chemical and mechanical stimulation through the release of cytokines and growth factors (2,3,15). Release of these signals during myocardial injury may regulate the extent of cardiac hypertrophy and fibrosis during the healing process (5, 15).Recent experiments suggest that cardiac fibroblasts also serve to relay electrical signals in the heart. When plated in primary culture, cardiac fibroblasts form physical interactions with cardiac myocytes through establishment of gap-junctional channels (6,8,14). With the use of a heterocellular culture model, it was established that fibroblasts are capable of relaying electrical excitation over distances as long as 300 m between strands of cardiac myocytes (14). However, the ionic mechanisms responsible for this electrical propagation are not well understoo...

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Partial cell fusion: A newly recognized type of communication between dedifferentiating cardiomyocytes and fibroblasts

Abstract: Our results suggest that the partial cell fusion-type of heterocellular communication in our co-culture model and the contacts observed in vivo may lead to new insights in cardiovascular disease.

Cited by 48 publications

References 37 publications

Structural remodelling of cardiomyocytes in the border zone of infarcted rabbit heart

Structural remodelling of cardiomyocytes in the border zone of infarcted rabbit heart

Genetic Control of Fusion Pore Expansion in the Epidermis ofCaenorhabditis elegans

Neonatal rat cardiac fibroblasts express three types of voltage-gated K⁺ channels: regulation of a transient outward current by protein kinase C

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Partial cell fusion: A newly recognized type of communication between dedifferentiating cardiomyocytes and fibroblasts

Abstract: Our results suggest that the partial cell fusion-type of heterocellular communication in our co-culture model and the contacts observed in vivo may lead to new insights in cardiovascular disease.

Cited by 48 publications

References 37 publications

Structural remodelling of cardiomyocytes in the border zone of infarcted rabbit heart

Structural remodelling of cardiomyocytes in the border zone of infarcted rabbit heart

Genetic Control of Fusion Pore Expansion in the Epidermis ofCaenorhabditis elegans

Neonatal rat cardiac fibroblasts express three types of voltage-gated K+ channels: regulation of a transient outward current by protein kinase C

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Neonatal rat cardiac fibroblasts express three types of voltage-gated K⁺ channels: regulation of a transient outward current by protein kinase C