Effective silencing of adhesion molecules on venous endothelial cells for protection of venous bypass grafts

Walker, Tobias; Muller, Isabelle S.; Raabe, Claudia; Nohé, Boris; Zanke, Christof; Ziemer, Gerhard; Wendel, Hans-Peter

doi:10.1016/j.ejcts.2011.01.076

Cited by 7 publications

(8 citation statements)

References 22 publications

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“…To measure velocities, images from these video sequences were digitalized at 25 frames/s, and the distance of movement of the MSC during the 10 s. interval was computed into pixels. All measurements were performed using customized software for image recognition as described previously (CellTracker, C. Zanke, University Hospital Tübingen, Germany) [34] .…”

Section: Methodsmentioning

confidence: 99%

Modulating endothelial adhesion and migration impacts stem cell therapies efficacy

Schäfer

Schwab

Siegel³

et al. 2020

EBioMedicine

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Background Limited knowledge of stem cell therapies` mechanisms of action hampers their sustainable implementation into the clinic. Specifically, the interactions of transplanted stem cells with the host vasculature and its implications for their therapeutic efficacy are not elucidated. We tested whether adhesion receptors and chemokine receptors on stem cells can be functionally modulated, and consequently if such modulation may substantially affect therapeutically relevant stem cell interactions with the host endothelium. Methods We investigated the effects of cationic molecule polyethylenimine (PEI) treatment with or without nanoparticles on the functions of adhesion receptors and chemokine receptors of human bone marrow-derived Mesenchymal Stem Cells (MSC). Analyses included MSC functions in vitro, as well as homing and therapeutic efficacy in rodent models of central nervous system´s pathologies in vivo. Findings PEI treatment did not affect viability, immunomodulation or differentiation potential of MSC, but increased the CCR4 expression and functionally blocked their adhesion receptors, thus decreasing their adhesion capacity in vitro. Intravenously applied in a rat model of brain injury, the homing rate of PEI-MSC in the brain was highly increased with decreased numbers of adherent PEI-MSC in the lung vasculature. Moreover, in comparison to untreated MSC, PEI-MSC featured increased tumour directed migration in a mouse glioblastoma model, and superior therapeutic efficacy in a murine model of stroke. Interpretation Balanced stem cell adhesion and migration in different parts of the vasculature and tissues together with the local microenvironment impacts their therapeutic efficacy. Funding Robert Bosch Stiftung, IZEPHA grant, EU grant 7 FP Health

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Section: Methodsmentioning

confidence: 99%

Modulating endothelial adhesion and migration impacts stem cell therapies efficacy

Schäfer

Schwab

Siegel³

et al. 2020

EBioMedicine

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“…Both siRNA were designed using the siRNA Target Finder software and synthesized by Qiagen (Hilden, Germany). Two independent siRNAs were used to obtain a selective reduction of E-Selectin expression: siRNA#1 [32] was synthesized by Qiagen and siRNA#2 [33] was purchased by Santa Cruz Biotechnology Inc. (sc-29296, Santa Cruz, CA). Control, non-silencing fluorescently labeled siRNA was obtained from Qiagen (AllStars Negative Control siRNA, Hilden, Germany).…”

Section: Methodsmentioning

confidence: 99%

TNFα Signals via p66Shc to Induce E-Selectin, Promote Leukocyte Transmigration and Enhance Permeability in Human Endothelial Cells

et al. 2013

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Endothelial cells participate in inflammatory events leading to atherogenesis by regulating endothelial cell permeability via the expression of VE-Cadherin and β-catenin and leukocyte recruitment via the expression of E-Selectins and other adhesion molecules. The protein p66Shc acts as a sensor/inducer of oxidative stress and may promote vascular dysfunction. The objective of this study was to investigate the role of p66Shc in tumor necrosis factor TNFα-induced E-Selectin expression and function in human umbilical vein endothelial cells (HUVEC). Exposure of HUVEC to 50 ng/ml TNFα resulted in increased leukocyte transmigration through the endothelial monolayer and E-Selectin expression, in association with augmented phosphorylation of both p66Shc on Ser36 and the stress kinase c-Jun NH2-terminal protein kinase (JNK)-1/2, and higher intracellular reactive oxygen species (ROS) levels. Overexpression of p66Shc in HUVEC resulted in enhanced p66Shc phosphorylation on Ser36, increased ROS and E-Selectin levels, and amplified endothelial cell permeability and leukocyte transmigration through the HUVEC monolayer. Conversely, overexpression of a phosphorylation-defective p66Shc protein, in which Ser36 was replaced by Ala, did not augment ROS and E-Selectin levels, nor modify cell permeability or leukocyte transmigration beyond those found in wild-type cells. Moreover, siRNA-mediated silencing of p66Shc resulted in marked reduction of E-Selectin expression and leukocyte transmigration. In conclusion, p66Shc acts as a novel intermediate in the TNFα pathway mediating endothelial dysfunction, and its action requires JNK-dependent phosphorylation of p66Shc on Ser36.

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“…The employed experimental strategies include the use of 1) pharmacological agents, such as lidocaine, which was studied in vitro using standard tissue bath techniques45; 2) gene targeting, e.g. short interfering RNA (siRNA)-mediated silencing of adhesion molecule46; and two additional methods that are elaborated hereunder: 3) vein harvesting, and 4) external stents.…”

Section: Methods To Extend Saphenous Vein Graft Patencymentioning

confidence: 99%

New Technologies in Coronary Artery Surgery

Taggart

Nir²,

Bolotin³

2013

RMMJ

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Coronary artery disease remains the leading cause of death in developed countries. Major recent studies such as SYNTAX and FREEDOM have confirmed that coronary artery bypass grafting (CABG) remains the gold standard treatment in terms of survival and freedom from myocardial infarction and the need for repeat revascularization. The current review explores the use of new technologies and future directions in coronary artery surgery, through 1) stressing the importance of multiple arterial conduits and especially the use of bilateral mammary artery; 2) discussing the advantages and disadvantages of off-pump coronary artery bypass; 3) presenting additional techniques, e.g. minimally invasive direct coronary artery bypass grafting, hybrid, and robotic-assisted CABG; and, finally, 4) debating a novel external stenting technique for saphenous vein grafts.

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Effective silencing of adhesion molecules on venous endothelial cells for protection of venous bypass grafts

Cited by 7 publications

References 22 publications

Modulating endothelial adhesion and migration impacts stem cell therapies efficacy

Modulating endothelial adhesion and migration impacts stem cell therapies efficacy

TNFα Signals via p66Shc to Induce E-Selectin, Promote Leukocyte Transmigration and Enhance Permeability in Human Endothelial Cells

New Technologies in Coronary Artery Surgery

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