Fibronectin expression during physiological and pathological cardiac growth

Farhadian, Farahnaz; Contard, F.; Corbier, Alain; Barrieux, A; Rappaport, L.; Samuel, J. L.

doi:10.1016/0022-2828(95)90067-5

Cited by 66 publications

(39 citation statements)

References 46 publications

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“…The function of laminin, another component of the BM, includes the mediation of adhesion, migration, growth and differentiation of cells. [18][19][20] Degradation of the BM proteins occurs under a variety of physiological and pathological circumstances including embryogenesis, 21 wound healing 22 and metastasis 23 by MMPs. It is known that MMP-2 is able to degrade type IV collagen and is upregulated during heart failure.…”

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Type IV collagen degradation in the myocardial basement membrane after unloading of the failing heart by a left ventricular assist device

Bruggink

Oosterhout

Jonge

et al. 2007

Laboratory Investigation

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After left ventricular assist device (LVAD) support in patients with end-stage cardiomyopathy, cardiomyocytes decrease in size. We hypothesized that during this process, known as reverse remodeling, the basement membrane (BM), which is closely connected to, and forms the interface between the cardiomyocytes and the extracellular matrix, will be severely affected. Therefore, the changes in the myocardial BM in patients with end-stage heart failure before and after LVAD support were studied. The role of MMP-2 in this process was also investigated. Transmission electron microscopy showed that the BM thickness decreased post-LVAD compared to pre-LVAD. Immunohistochemistry indicated a reduced immunoreactivity for type IV collagen in the BM after LVAD support. Quantitative PCR showed a similar mRNA expression for type IV collagen pre-and post-LVAD. MMP-2 mRNA almost doubled post-LVAD (Po0.01). In addition, active MMP-2 protein as identified by gelatin zymography and confirmed by Western blot analysis was detected after LVAD support and in controls, but not before LVAD support. Active MMP was localized in the BM of the cardiomyocyte, as detected by type IV collagen in situ zymography. Furthermore, in situ hybridization/immunohistochemical double staining showed that MMP-2 mRNA was expressed in cardiomyocytes, macrophages, T-cells and endothelial cells. Taken together, these findings show reduced type IV collagen content in the BM of cardiomyocytes after LVAD support. This reduction is at least in part the result of increased MMP-2 activity and not due to reduced synthesis of type IV collagen. Left ventricular assist devices (LVADs) are commonly used in patients with heart failure as a bridge to heart transplantation (HTx). In most cases, LVAD support extends the patient's lifespan and improves the quality of life. 1,2 In addition, pressure and volume unloading of the left ventricle (LV) by LVAD can reverse left ventricular dilatation and leads to regression of left ventricular hypertrophy and neurohormonal changes. [3][4][5][6] The understanding of this process, referred to as 'reverse remodeling,' 7 is important for a better insight into both myocardial events during LVAD support and the processes leading to heart failure. Additionally, several institutions described the possibility of LVAD explantation without the need for HTx (weaning). 4,[8][9][10][11] This requires a profound knowledge of the process of reverse remodeling.In previous studies with cardiac unloading, we demonstrated partial recovery of the contractile myofilaments in the cardiomyocytes 12 and decreased natriuretic peptide levels both in the plasma of the patients and in the heart. 5,6 Since reverse remodeling not only involves the cardiomyocytes but also the extracellular matrix (ECM), we have focused on the changes in ECM before and after LVAD support. The ECM, which consists of the fibrillar collagens, type I and III collagen, and comprises a basement membrane (BM) surrounding cardiomyocytes, forms a continuum between different cell types within t...

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confidence: 99%

Type IV collagen degradation in the myocardial basement membrane after unloading of the failing heart by a left ventricular assist device

Bruggink

Oosterhout

Jonge

et al. 2007

Laboratory Investigation

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“…Altered expression of collagens, fibronectin, osteopontin, tenacin, and other ECM components have been documented. [57][58][59][60][61][62][63][64] The expression of specific integrins has not been examined extensively in all of these examples, but when studied, integrins also show an altered pattern. However, it is not clear whether the altered integrin localization is a primary response or one commensurate with the changes in ECM component(s).…”

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Integrins and the Myocardium

Ross

Borg

2001

Circulation Research

397

279

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Abstract-Extracellular matrix provides a structural, chemical, and mechanical substrate that is essential in cardiac development, growth, and responses to pathophysiological signals. Transmembrane receptors termed integrins provide a dynamic interaction of environmental cues and intracellular events. Integrins orchestrate multiple functions in the intact organism including organogenesis, regulation of gene expression, cell proliferation, differentiation, migration, and death. They are expressed in all cellular components of the cardiovascular system, including the vasculature, blood, cardiac myocytes and nonmuscle cardiac cells. The focus of this review will be on the role of integrins in the myocardium. We will provide background on integrin structure and function, discuss how the expression of integrins is critical to the form and function of the developing and postnatal myocardium, and review the known data on integrins as signaling molecules in the heart. Finally, we will offer insights to the future research directions into this important family of extracellular matrix receptors in the myocardium. Key Words: integrin Ⅲ myocardium Ⅲ extracellular matrix E xtracellular matrix (ECM) provides a structural, chemical, and mechanical substrate that is essential in cardiac development, growth, and responses to pathophysiological signals. Transmembrane receptors termed integrins provide a dynamic interaction of environmental cues and intracellular events. [1][2][3] Integrins orchestrate multiple functions in the intact organism including organogenesis, regulation of gene expression, cell proliferation, differentiation, migration, and death. They are expressed in all cellular components of the cardiovascular system, including the vasculature, blood, cardiac myocytes, and nonmuscle cardiac cells. The focus of this review will be on the role of integrins in the myocardium, because their function in the vasculature and platelets has been recently reviewed. 4,5 We will discuss how the expression of integrins is critical to the form and function of the myocardium, evaluate potential mechanisms of action of the integrins in the regulation of these processes, and offer insights to the future research directions into this important family of ECM receptors in the myocardium. Integrin StructureIntegrins are noncovalently associated heterodimeric transmembrane receptors composed of ␣ and ␤ subunits, with ␣ subunits ranging from 120 to 180 kDa whereas ␤ subunits are 90 to 110 kDa. 3,6 Historically, integrins were identified based on an initial series of experiments suggesting a physical association between fibronectin and the intracellular cytoskeleton. 7 Subsequently, studies were published from several laboratories that (1) identified glycoproteins having characteristics of membrane proteins, and (2) showed that antibodies which recognized these proteins could inhibit cellular adhesion. 8 -12 These observations led to the cloning of chick fibroblast cDNAs that encoded for a molecule involved in transmembrane linkage between f...

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“…Culturing noncardiac cells on stiff substrates tips the balance of adhesion in favor of focal adhesions and away from cell-cell adhesions (30)(31)(32), suggesting that mechanical forces can modulate the assembly or disassembly of tissues. Many cardiomyopathies are characterized by increased fibrosis and tissue stiffening (33,34), suggesting that cardiac myocytes might be similarly sensitive to tissue compliance and favor focal adhesion formation over cell-cell junction formation in a fibrotic microenvironment.…”

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Cooperative coupling of cell-matrix and cell–cell adhesions in cardiac muscle

McCain

Lee

Aratyn-Schaus

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

159

162

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Adhesion between cardiac myocytes is essential for the heart to function as an electromechanical syncytium. Although cell-matrix and cell-cell adhesions reorganize during development and disease, the hierarchical cooperation between these subcellular structures is poorly understood. We reasoned that, during cardiac development, focal adhesions mechanically stabilize cells and tissues during myofibrillogenesis and intercalated disc assembly. As the intercalated disc matures, we postulated that focal adhesions disassemble as systolic stresses are transmitted intercellularly. Finally, we hypothesized that pathological remodeling of cardiac microenvironments induces excessive mechanical loading of intercalated discs, leading to assembly of stabilizing focal adhesions adjacent to the junction. To test our model, we engineered μtissues composed of two ventricular myocytes on deformable substrates of tunable elasticity to measure the dynamic organization and functional remodeling of myofibrils, focal adhesions, and intercalated discs as cooperative ensembles. Maturing μtissues increased systolic force while simultaneously developing into an electromechanical syncytium by disassembling focal adhesions at the cell-cell interface and forming mature intercalated discs that transmitted the systolic load. We found that engineering the microenvironment to mimic fibrosis resulted in focal adhesion formation adjacent to the cell-cell interface, suggesting that the intercalated disc required mechanical reinforcement. In these pathological microenvironments, μtissues exhibited further evidence of maladaptive remodeling, including lower work efficiency, longer contraction cycle duration, and weakened relationships between cytoskeletal organization and force generation. These results suggest that the cooperative balance between cell-matrix and cell-cell adhesions in the heart is guided by an architectural and functional hierarchy established during development and disrupted during disease.adherens junctions | sarcomere | mechanotransduction | extracellular matrix I n the adult heart, healthy ventricular tissue is characterized by spatial segregation of cell-matrix adhesions to transverse myocyte borders (1) and cell-cell adhesions to longitudinal myocyte borders (2). Many cardiomyopathies are characterized by lateralization of cell-cell adhesions (3-5), increased expression of cell-matrix adhesions (6, 7), and arrhythmogenesis (8), suggesting that spatially organized adhesion is essential for effective eletromechanical coupling (9). Although in vivo studies have shown that localization of cell-matrix and cell-cell adhesions is developmentally regulated (10-13), the factors that regulate their assembly and disassembly are not well understood.Cell-matrix adhesions are especially important during organogenesis, anchoring developing cells and tissues to the extracellular matrix (ECM) (14) and directing cell migration (15-17). As development progresses, cell-matrix adhesions must selectively disassemble so that cell-cell adhesions can f...

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Fibronectin expression during physiological and pathological cardiac growth

Cited by 66 publications

References 46 publications

Type IV collagen degradation in the myocardial basement membrane after unloading of the failing heart by a left ventricular assist device

Type IV collagen degradation in the myocardial basement membrane after unloading of the failing heart by a left ventricular assist device

Integrins and the Myocardium

Cooperative coupling of cell-matrix and cell–cell adhesions in cardiac muscle

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