Comparative assessment of intimal hyperplasia development after 14 days in two different experimental settings: Tissue culture versus ex vivo continuous perfusion of human saphenous vein

Rey, Julian; Probst, H.; Mazzolai, Lucia; Bosman, Fred T.; Pusztaszeri, Marc; Stergiopulos, Nikolaos; Ris, Hans‐Beat; Hayoz, Daniel; Saucy, François; Corpataux, Jean-Marc

doi:10.1016/j.jss.2004.04.003

Cited by 14 publications

(12 citation statements)

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“…In addition, PAI-1 plays a key role in determining proliferation response to vascular injury by inhibiting the degradation of fibrin and several extracellular matrix proteins by plasmin [11] . Our previous studies have shown that the ex vivo vein support system (EVVSS) allows to study vascular wall remodeling up to 14 days in a low continuous laminar flow setting under reproducible and standardized conditions [12,13] . We hypothesized that the same observation could be demonstrated in our modified pulsatile ex vivo perfusion system, characterized by the presence of high shear stress conditions, pulsatile flow and high intraluminal pressure applied to the veins to create physiological arterial conditions.…”

Section: Ex Vivo Pulsatile Perfusion Of Human Saphenousmentioning

confidence: 99%

“…We previously described an ex vivo vein system, in which venous segments were perfused in a continuous laminar unidirectional flow with low levels of shear stress [12,13] . The vein system was modified in order to generate pulsatile perfusion induced by a gearing pump (Reglo-Z, Ismatec , Zurich, Switzerland), along with a unidirectional head pump, inducing a 4-to 420-ml/min flow velocity.…”

Section: Ex Vivo Vein Perfusion Systemmentioning

confidence: 99%

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Ex vivo Pulsatile Perfusion of Human Saphenous Veins Induces Intimal Hyperplasia and Increased Levels of the Plasminogen Activator Inhibitor 1

et al. 2010

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Vessel wall trauma induces vascular remodeling processes including the development of intimal hyperplasia (IH). To assess the development of IH in human veins, we have used an ex vivo vein support system (EVVSS) allowing the perfusion of freshly isolated segments of saphenous veins in the presence of a pulsatile flow which reproduced arterial conditions regarding shear stress, flow rate and pressure during a period of 7 and 14 days. Compared to the corresponding freshly harvested human veins, histomorphometric analysis showed a significant increase in the intimal thickness which was already maximal after 7 days of perfusion. Expression of the endothelial marker CD31 demonstrated the presence of endothelium up to 14 days of perfusion. In our EVVSS model, the activity as well as the mRNA and protein expression levels of plasminogen activator inhibitor 1, the inhibitor of urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA), were increased after 7 days of perfusion, whereas the expression levels of tPA and uPA were not altered. No major change was observed between 7 and 14 days of perfusion. These data show that our newly developed EVVSS is a valuable setting to study ex vivo remodeling of human veins submitted to a pulsatile flow.

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Section: Ex Vivo Pulsatile Perfusion Of Human Saphenousmentioning

confidence: 99%

Section: Ex Vivo Vein Perfusion Systemmentioning

confidence: 99%

Ex vivo Pulsatile Perfusion of Human Saphenous Veins Induces Intimal Hyperplasia and Increased Levels of the Plasminogen Activator Inhibitor 1

et al. 2010

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“…However, this finding will be the basis for our further studies to develop ex vivo continuous perfusion of human vessel segments for studying atherosclerosis. This ex vivo model has more advantages because the changes of the whole vascular wall under flow conditions and longer time of study can be observed in serial section by histopathology, immunohistochemistry 45 and ultrastructural pathology. In conclusion, (i) the tight junction of the HUVEC in the model was the most important criterion for evaluating the early pathologic changes; and (ii) our basic atherosclerosis model showed feasibility to modify ex vivo vein culture for pharmacological studies in atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Improvement of Function and Morphology of Tumor Necrosis Factor-.ALPHA. Treated Endothelial Cells With 17-.BETA. Estradiol A Preliminary Study for a Feasible Simple Model for Atherosclerosis

Suwannaprapha

Chaisri

Riyong

et al. 2005

Circ J

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n normal vasculature endothelial cells (EC), a small amount of NO synthesized by endothelial nitric oxide synthase (eNOS) maintains normal vascular physiological function controls. 1,2 Endothelial cell dysfunction in eNOS expression by tumor necrosis factor-(TNF-) is involved in the pathogenesis of vascular diseases, for example atherosclerosis. 3 The related pathologic changes are increased expression of adhesion molecules, including intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, and E-selectin that enhances inflammatory cell infiltration in the vascular wall, platelet aggregation and adhesion on EC surfaces, and smooth muscle cell proliferation and migration. 1,4 In contrast, 17-estradiol (E2) upregulates eNOS production in EC, protects against atherosclerosis and recovers EC after arterial injury in animal models. [5][6][7] At present, experimental models for pathological and pharmacological studies in atherosclerosis have been developed only in laboratory models, eg, primates, rats and mice. 5,6,8 The important defects in the animal models are their complicated metabolisms with systemic variation and the difficulty of controlling the concentrations of drugs acting directly on the target cells. To date, no in vitro vascular model has been demonstrated for pharmacological studies in atherosclerosis, even though there have been several studies with other vascular diseases. [9][10][11] In the present study, we first constructed the in vitro model vascular wall with endothelial cell dysfunction in eNOS production by TNF-to mimic the important basic early stage pathology of atherosclerosis, and determined the potential of the model by using E2 as an antiatheroslerogenic agent. Methods Endothelial Cell CultureHuman umbilical vein endothelial cells (HUVEC) were separated from fresh umbilical cord veins, as previously described. 12 The HUVEC were cultured in human endothelial-SFM basal growth medium (Gibco BRL, Gaithersburg, MD, USA) supplemented with 10% heat-inactivated fetal bovine serum (FBS), 40 g/ml gentamycin and glutamine. The HUVEC were incubated at 37°C in a 5% CO2 atmosphere. Positive staining for CD31 confirmed the endothe- Background Dysfunction of endothelial cells (EC) to produce endothelial nitric oxide synthase (eNOS) by tumor necrosis factor-(TNF-) causes critical features of vascular inflammation associated with several disease states (eg, atherosclerosis including increased platelet aggregation and adhesion on EC, elevated adhesion molecules and enhanced inflammatory cells binding to EC). 17-estradiol (E2) can stimulate eNOS production and improve the critical features of atherosclerosis. Using TNF-and E2, we attempted to develop an in vitro vascular model for studying atherosclerosis. Methods and ResultsHuman umbilical vein endothelial cells (HUVEC) grown in transwells were cocultured with smooth muscle cells in a 24-well plate to mimic the major components of the vascular wall. The model was incubated with TNF-(10 ng/ml) for 12 h, prior exposed to E2 (100 pg/ml) f...

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“…Other systems have been reported which were designed without the ability to accurately simulate the higher frequency content of the physiologic arterial pressure or flowrate waveforms. They instead were designed to generate certain desired static [256][257][258][259][260] or oscillatory [81,142,[261][262][263][264][265][266][267][268][269][270] signals for the purpose of estimating the biomechanical properties of blood vessel segments.…”

Section: The Concept Of Ex Vivo Perfusion Was Originally Investigatedmentioning

confidence: 99%

In Situ Bioengineering of Arterial Vein Grafts

El-Kurdi

Morelli

Hong

et al. 2008

ASME 2008 Summer Bioengineering Conference, Parts a and B

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The autogenous saphenous vein remains the graft of choice for both coronary (500,000 annually in the US) and peripheral (80,000 annually) arterial bypass procedures. Failure of arterial vein grafts (AVGs) remains a major problem, and patients with failed grafts will die or require reoperation. Intimal hyperplasia (IH) accounts for 20% to 40% of all AVG failures. It is believed that this adverse pathological response by AVGs is largely due to their abrupt exposure to the significantly elevated circumferential wall stress (CWS) associated with the arterial system. We believe that if an AVG is given an ample opportunity to adapt and remodel to the stresses of its new environment, cellular injury may be reduced, thus limiting the initiating mechanisms of IH.The goal of this work was to develop a new mechanical conditioning paradigm, in the form of a peri-adventitially placed, biodegradable polymer wrap, to safely and functionally "arterialize" AVGs in situ. The polymer wrap was tuned so that as it degraded over a desired period of time, the mechanical support offered by it was reduced and the vein was exposed to gradually increasing levels of CWS in situ.To investigate the effects of mechanical conditioning on AVGs, we utilized both our well established, validated ex vivo vascular perfusion system (EVPS) as well as an appropriate preclinical animal model. The "engineering" component of this bioengineering study was to enhance our EVPS capabilities. Enhancements were made in the form of rigorous mathematical modeling, via subspace system identification, and automatic feedback control, via proportional iv integral and derivative control, of the arterial CWS and shear stress waveform generation capabilities of the EVPS. Pairs of freshly harvested porcine internal jugular veins (PIJVs) were perfused ex vivo under several biomechanical conditions. The acute hyperplastic response of PIJVs abruptly exposed to arterial hemodynamic conditions was compared to PIJVs perfused under normal venous conditions. In an attempt to attenuate this acute hyperplastic response, an ex vivo mechanical conditioning paradigm was imposed onto the PIJVs both via manual adjustment of EVPS parameters and via an adventitially placed tuned electrospun biodegradable polymer wrap. Early markers of IH were evaluated post-perfusion, and they included vascular smooth muscle cell apoptosis, proliferation, and phenotypic modulation. Quantification of these markers via immunohistochemical techniques provided the foundation for the final stage of this work. To assess the efficacy of the tuned electrospun biodegradable polymer wrap in attenuating the development of intimal hyperplasia in AVGs, a series of preclinical studies was performed in a pig model. PIJVs abruptly exposed to arterial levels of CWS showed a significant increase in apoptosis and in the number of synthetic smooth muscle cells, as well as a decrease in proliferation. Mechanical conditioning, via both manual adjustment of the EVPS parameters and placement of the biodegradable adventitial wra...

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Comparative assessment of intimal hyperplasia development after 14 days in two different experimental settings: Tissue culture versus ex vivo continuous perfusion of human saphenous vein

Cited by 14 publications

References 35 publications

Ex vivo Pulsatile Perfusion of Human Saphenous Veins Induces Intimal Hyperplasia and Increased Levels of the Plasminogen Activator Inhibitor 1

Ex vivo Pulsatile Perfusion of Human Saphenous Veins Induces Intimal Hyperplasia and Increased Levels of the Plasminogen Activator Inhibitor 1

Improvement of Function and Morphology of Tumor Necrosis Factor-.ALPHA. Treated Endothelial Cells With 17-.BETA. Estradiol A Preliminary Study for a Feasible Simple Model for Atherosclerosis

In Situ Bioengineering of Arterial Vein Grafts

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