Association of smooth muscle cell phenotypic modulation with extracellular matrix alterations during neointima formation in rabbit vein grafts

Zhang, Weida; Bai, Hong-zhi; Sawa, Yoshiki; Yamakawa, Tomoyuki; Kadoba, Keishi; Taniguchi, Kazuhiro; Masuda, Junichi; Ogata, Jun; Shirakura, R; Matsuda, Hikaru

doi:10.1016/s0741-5214(99)70189-8

Cited by 50 publications

(29 citation statements)

References 42 publications

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“…The observed alteration in SMC phenotype that resulted from exposing PIJVs to ART conditions agrees with previously reported data [71,131,163]. The concept of more gradual imposition of arterial levels of CWS to AVGs has not previously been reported but could result in a means to slow down or inhibit SMC phenotypic modulation which could consequently attenuate the hyperplastic response.…”

Section: Discussionsupporting

confidence: 90%

“…Balloon inflation injury to the media was shown to promote ECM synthesis by SMCs as well as to decrease alpha actin content [162]. Several reports have shown that neointimal SMCs of veins transposed to the arterial circulation are phenotypically altered [71,131,163], supporting the notion that the change from the venous to the arterial environment triggers phenotypic alteration. Further evidence comes from ex vivo organ culture studies where, for example, cyclic stretch was found to be necessary to maintain the contractile function of SMCs in cultured rat portal veins [164].…”

Section: Phenotypic Modulationmentioning

confidence: 89%

“…However, 48 hours after arterial injury, 15-40% of SMCs are mitotic [152]. This abrupt shift in functionality is AVGs exhibit neointimal formation within the first two months by the migration and proliferation of synthetic SMCs [131] and by subsequent, sustained ECM accumulation, including type I collagen production, in the prolonged presence of the de-differentiated type SMCs.…”

Section: Phenotypic Modulationmentioning

confidence: 99%

“…The phenotypic modulation of SMCs associated with vein grafting has been shown to alter ECM synthesis characterized by increasing collagen type I and elastin production [130,131]. Veins used as arterial bypass grafts undergo an alteration of their ECM components [225], which can result in a loss of lumenal area and eventual occlusion [15,226].…”

Section: Remodelingmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 90%

Section: Phenotypic Modulationmentioning

confidence: 89%

Section: Phenotypic Modulationmentioning

confidence: 99%

Section: Remodelingmentioning

confidence: 99%

See 2 more Smart Citations

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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show abstract

“…For example, balloon inflation injury to the media was shown to promote extracellular matrix synthesis and decrease ␣-actin content in SMCs [156]. Zhang et al showed that neointimal smooth muscle cells of external jugular veins transposed to the carotid artery position display a more primitive synthetic phenotype [157], supporting the notion that the change from the venous to the arterial biomechanical milieu triggers phenotypic alteration. Further evidence comes from ex vivo organ culture studies wherein cyclic stretch was found to be necessary to maintain the contractile function of SMCs in cultured rat portal veins [158].…”

Section: Lipid Accumulationmentioning

confidence: 98%

Mechanopathobiology of Atherogenesis: A Review

VanEpps

Vorp

2007

Journal of Surgical Research

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Development of tissue engineered vascular grafts and application of nanomedicine

Rathore

Cleary

Naito

et al. 2012

WIREs Nanomed Nanobiotechnol

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Vascular Tissue Engineering belongs to a rapidly expanding discipline. Tissue engineered vascular grafts (TEVG) have a broad range of clinical application extending from use as small diameter vascular grafts in adult peripheral vasculature to serving as large vessel conduits in pediatric cardiovascular surgery. Several approaches have been utilized by different groups to design these grafts. Preliminary outcomes are exceedingly promising. These grafts have demonstrated the ability to transform into living blood vessels with growth potential and while the underlying mechanisms remain to be elucidated, it has been shown that inflammatory pathways may play an important role. Small animal experiments, development of cell seeding techniques and the application of nanotechnology have all contributed vastly to our understanding of the mechanisms involved in TEVG remodeling. The application of nanomedicine in TEVG design continues to expand at a rapid rate and has provided some clues as to how vascular graft design can be pursued in the future. In this review we discuss the current state of the field of tissue engineered vascular grafts and how the principles of nanomedicine are being applied to aid in the design of second-generation grafts.

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Association of smooth muscle cell phenotypic modulation with extracellular matrix alterations during neointima formation in rabbit vein grafts

Cited by 50 publications

References 42 publications

In Situ Bioengineering of Arterial Vein Grafts

In Situ Bioengineering of Arterial Vein Grafts

Mechanopathobiology of Atherogenesis: A Review

Development of tissue engineered vascular grafts and application of nanomedicine

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