Zyxin Mediation of Stretch-Induced Gene Expression in Human Endothelial Cells

Wójtowicz, Agnieszka; Babu, Sahana Suresh; Li, Li; Gretz, Norbert; Hecker, Markus; Cattaruzza, Marco

doi:10.1161/circresaha.110.227850

Cited by 57 publications

(78 citation statements)

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“…Exposure of HUVECs to cyclical stretch causes nuclear migration of zyxin (a zinc finger protein), which acts to coordinate the expression of proinflammatory genes such as interleukin (IL)-8, vascular cell adhesion molecule (VCAM) and intercellular adhesion molecule (ICAM) [73]. Similarly, an upregulation of inflammatory mediators, including IL-8 and MCP, has been seen in HUVECs in response to cyclical stretch [74].…”

Section: Stretch-regulated Genes Affecting the Inflammatory Response mentioning

confidence: 99%

The Effect of Pressure-Induced Mechanical Stretch on Vascular Wall Differential Gene Expression

et al. 2012

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High blood pressure is responsible for the modulation of blood vessel morphology and function. Arterial hypertension is considered to play a significant role in atherosclerotic ischaemic heart disease, stroke and hypertensive nephropathy, whereas high venous pressure causes varicose vein formation and chronic venous insufficiency and contributes to vein bypass graft failure. Hypertension exerts differing injurious forces on the vessel wall, namely shear stress and circumferential stretch. Morphological and molecular changes in blood vessels ascribed to elevated pressure consist of endothelial damage, neointima formation, activation of inflammatory cascades, hypertrophy, migration and phenotypic changes in vascular smooth muscle cells, as well as extracellular matrix imbalances. Differential expression of genes encoding relevant factors including vascular endothelial growth factor, endothelin-1, interleukin-6, vascular cell adhesion molecule, intercellular adhesion molecule, matrix metalloproteinase-2 and -9 and plasminogen activator inhibitor-1 has been explored using ex vivo cellular or organ stretch models and in vivo experimental animal models. Identification of pertinent genes may unravel new therapeutic strategies to counter the effects of pressure-induced stretch on the vessel wall and hence minimise its notable complications.

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Section: Stretch-regulated Genes Affecting the Inflammatory Response mentioning

confidence: 99%

The Effect of Pressure-Induced Mechanical Stretch on Vascular Wall Differential Gene Expression

et al. 2012

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“…Hypertension is associated with dysfunctional vascular endothelium and thickening of the smooth muscle layer around the vessel [40,41]. Endothelial Nitric Oxide Synthase (eNOS) expressed in endothelium of blood vessels and heart, plays a role in cardiovascular homeostasis, both under physiological condition and in response to stress [42].…”

Section: Role Of Rsps In Cardiovascular Pathologiesmentioning

confidence: 99%

“…Vascular endothelial cells play a critical role in several biological processes like permeability, clotting, inflammation, angiogenesis, and regeneration of the injured tissue [59,41]. Endothelial dysfunction is a hallmark of vascular complications that has been shown to be predictive of future cardiovascular pathological events [41].…”

Section: Role Of Rsps In Cardiovascular Pathologiesmentioning

confidence: 99%

“…Endothelial dysfunction is a hallmark of vascular complications that has been shown to be predictive of future cardiovascular pathological events [41]. Under mechanical and biomechanical stress, HuR has been shown to induce inflammatory response in human umbilical vein endothelial cells by regulating the expression of stress-sensitive genes such as such as Kruppel-like factor 2 (Klf2), eNOS, and bone morphogenic protein 4 (BMP-4) [60].…”

Section: Role Of Rsps In Cardiovascular Pathologiesmentioning

confidence: 99%

“…HuR also promotes endothelial activation by enhancing the stability of ICAM-1 (Intercellular Adhesion Molecule) and VCAM-1 (Vascular Cell Adhesion molecule), thus increasing leukocyte-endothelial cell adhesion [61]. ICAM-1 and VCAM-1 are cell surface glycoproteins that play a critical role in inflammation by stabilizing cell-cell interactions and facilitating leukocyte endothelial transmigration [40,41]. …”

Section: Role Of Rsps In Cardiovascular Pathologiesmentioning

confidence: 99%

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RNA-stabilizing proteins as molecular targets in cardiovascular pathologies

Babu

Joladarashi

Jeyabal

et al. 2015

Trends in Cardiovascular Medicine

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The stability of mRNA has emerged as a key step in the regulation of eukaryotic gene expression and function. RNA stabilizing proteins (RSPs) contain several RNA recognition motifs, and selectively bind to Adenylate- and uridylate- Rich Elements in the 3′ untranslated region of several mRNAs leading to altered processing, stability and translation. These post-transcriptional gene regulations play a critical role in cellular homeostasis; therefore act as molecular switch between ‘normal cell’ and ‘disease state’. Many mRNA binding proteins have been discovered to date, which either stabilize (HuR/HuA, HuB, HuC, HuD) or destabilize (AUF1, Tristetraprolin, KSRP) the target transcripts. Although the function of RSPs has been widely studied in cancer biology, its role in cardiovascular pathologies is only beginning to evolve. The current review provides an overall understanding of the potential role of RSP, specifically HuR-mediated mRNA stability in myocardial infarction, hypertension and hypertrophy. Also, the effect of RSPs on various cellular processes including inflammation, fibrosis, angiogenesis, cell-death and proliferation and its relevance to cardiovascular pathophysiological processes is presented. We also discuss the potential clinical implications of RSPs as therapeutic targets in cardiovascular diseases.

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Bioreactors for Tissue Engineering

Birla

2014

Introduction to Tissue Engineering

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Tissue Engineering 324 Use of Bioreactors in Tissue EngineeringA tissue engineering bioreactor can be defined as a device that uses mechanical means to influence biological processes . Bioreactors can be used to aid in the in vitro development of new tissue by providing biochemical and physical regulatory signals to cells and encouraging them to undergo differentiation and/or to produce extracellular matrix prior to in vivo implantation. Bioreactors are devices in which biological or biochemical processes develop under a closely monitored and tightly controlled environment. Cells respond to mechanical stimulation and bioreactors can be used to apply mechanical stimulation to cells. This can encourage cells to produce extracellular matrix (ECM) in a shorter time period and in a more homogeneous manner than would be the case with static culture. For example, in comparisons between ECM protein levels of equine articluar chondrocytes cultured on polyglycolic acid scaffolds after 5 weeks in culture, constructs cultured under hydrostatic pressure showed significant improvements over constructs cultured in static medium (Carver & Heath, 1999). A benefit of ECM production is the increase in mechanical stiffness that it provides to the construct. A six-fold increase in equilibrium aggregate modulus (an intrinsic property of cartilage which is a measure of stiffness) was found after 28 days of culture in a compression bioreactor compared to free swelling controls (Mauck, et al., 2000). Another important application of bioreactors is in cellular differentiation. Mechanical stimulation can be used to encourage stem cells down a particular path and hence provide the cell phenotype required. Bioreactors can provide biochemical and physical regulatory signals that guide differentiation (Altman, et al., 2002). There is great potential for using mesenchymal stem cells and other multipotent cells to generate different cell types and bioreactors can play an important role in this process. As well as providing mechanical stimulation, bioreactors can also be used to improve cellular spatial distribution. A heterogeneous cell distribution is a major obstacle to developing any three-dimensional tissue or organ in vitro. Defects requiring tissue engineering solutions are typically many millimetres in size (Goldstein, et al., 2001). Scaffolds in such a size range are easily fabricated, however, problems arise when culturing cells on these scaffolds. As the size of the scaffold increases, diffusion of nutrients to the centre of the construct becomes more difficult. Static culture conditions result in scaffolds with few cells in the centre of the construct (Cartmell, et al., 2003). It is hypothesised that this is due to limited cell penetration during seeding, cell migration to the scaffold periphery during culture, or cell death in the centre of the scaffold (

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Zyxin Mediation of Stretch-Induced Gene Expression in Human Endothelial Cells

Cited by 57 publications

References 14 publications

The Effect of Pressure-Induced Mechanical Stretch on Vascular Wall Differential Gene Expression

The Effect of Pressure-Induced Mechanical Stretch on Vascular Wall Differential Gene Expression

RNA-stabilizing proteins as molecular targets in cardiovascular pathologies

Bioreactors for Tissue Engineering

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