Neointimal Hyperplasia after Stenting in a Human Mammary Artery Organ Culture

Guérin, Patrice; Rondeau, Felix; Grimandi, G.; Heymann, Marie-Françoise; Heymann, Diana; Pillet, Paul; Habash, Oussama Al; Loirand, Gervaise; Pacaud, Pierre; Crochet, D.

doi:10.1159/000076245

Cited by 21 publications

(14 citation statements)

References 24 publications

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“…However, quantitatively, there is no perfect correlation between RhoA activity, p27 levels and the mitotic activity in the arterial wall [20]. This observation suggests that other regulators of the cell cycle might participate in the control of cell proliferation involved in the neointima formation.…”

Section: Discussionmentioning

confidence: 99%

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Stent Implantation Activates RhoA in Human Arteries: Inhibitory Effect of Rapamycin

Guérin

Sauzeau²,

Rolli–Derkinderen³

et al. 2005

J Vasc Res

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In-stent restenosis is a novel pathobiologic process resulting from vascular smooth muscle cell (VSMC) proliferation, migration and excessive matrix production. The present study was designed to assess the activity of RhoA, a major regulator of VSMC proliferation and migration, after stenting and to determine its role in the neointimal formation. Analysis of RhoA activity in an ex vivo organ culture model of human internal mammary arteries demonstrates that stenting induced a time-dependent increase in RhoA activity (4.9 ± 0.4 vs. 1.2 ± 0.2 in control at 28 days, n = 4, p < 0.0001) associated with a concomitant decrease in p27 expression. Treatment of stented arteries with the permeant RhoA inhibitor TAT-C3 (10 µg/ml) or Rho-kinase inhibitors (Y-27632, 10 µmol/l; fasudil, 10 µmol/l) inhibited both neointimal formation and decrease in p27 expression. Rapamycin (1 and 10 nmol/l) also inhibited neointimal formation, and induced a loss of RhoA expression. The inhibitory effect of rapamycin on neointimal thickening is prevented by the dominant active form of RhoA. Our study shows that stent implantation induces maintained RhoA activation and demonstrates that the inhibitory action of rapamycin on RhoA expression plays a key role in its antirestenotic effect.

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Section: Discussionmentioning

confidence: 99%

“…Stenting and organ culture were performed as previously described [20]. Briefly, unused segments of internal mammary arteries (2–3 cm long) were obtained from patients undergoing coronary bypass surgery.…”

Section: Methodsmentioning

confidence: 99%

Stent Implantation Activates RhoA in Human Arteries: Inhibitory Effect of Rapamycin

Guérin

Sauzeau²,

Rolli–Derkinderen³

et al. 2005

J Vasc Res

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“…Arterial segments measuring approximately 2 cm were subjected to balloon dilatation (3ϫ30 s, 10 ATM) followed by stent implantation by 30 s inflation at 10 ATM, as previously described. 17 The stented arterial samples were subsequently cultured in serum-containing medium for 14 days at 37°C in 95% air/5% CO 2 in the absence or presence of LTB 4 (100 nmol/L), with change of medium every 2 days. Morphological analysis of intimal hyperplasia was performed as described above.…”

Section: Human Artery Organ Culturementioning

confidence: 99%

Leukotriene Receptor Antagonism and the Prevention of Extracellular Matrix Degradation During Atherosclerosis and In-Stent Stenosis

Hlawaty

Jacob

Louedec

et al. 2009

ATVB

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Objective-The lipid-derived inflammatory mediators leukotrienes (LTs) are produced during vascular injury. The aim of the present study was to determine the role of LT receptor signaling in the pathophysiology of in-stent stenosis. Methods and Results-New Zealand White rabbits were fed 0.3% cholesterol and subjected to angioplasty with balloon dilatation and stent implantation in the right carotid artery. Rabbits treated for 2 weeks with the BLT receptor antagonist BIIL284 (3 mg/kg once daily by oral gavage) displayed a significantly reduced in-stent intimal hyperplasia in carotid arteries compared with vehicle-treated rabbits. In addition, BIIL284 treatment significantly reduced the extracellular matrix metalloproteinase (MMP)-2 and MMP-9 activities in stented arteries. The inhibited MMP-9 activity was correlated with decreased macrophage content in the lesions. The LTB 4 -induced migration of vascular smooth muscle cells was significantly inhibited by transfection with siRNA against MMP-2. Finally, human arteries subjected to ex vivo angioplasty and stent implantation displayed an increased in-stent intimal hyperplasia and higher MMP-2 and -9 activities in the presence of LTB 4 . T he use of stents in percutaneous coronary interventions (PCI) has reduced the incidence of restenosis, particularly in combination with local administration of cell cycle inhibiting rapamycin derivates by means of drug eluting stents (DES). However, the use of DES in interventional cardiology has also been associated with an increased risk of late stent thrombosis. 1 Such side-effects suggest the importance of identifying novel targets for both local and systemic treatment, which have an inhibitory effect on in-stent restenosis. Conclusions-TheseInterestingly, PCI is a stimulus for intracoronary formation of leukotrienes (LTs). 2 Derived from arachidonic acid though the 5-lipoxygenase (5-LO) pathway, LTs are potent inflammatory mediators implicated in several pathophysiological processes associated with atherosclerosis. 3 Furthermore, the polymorphisms within the gene encoding the 5-LO activating protein (FLAP), which have been associated with an increased risk of myocardial infarction and stroke, 4 were recently reproduced in restenosis patients. 5 In the latter study, 2 of the FLAP gene polymorphisms studied were independent prognostic factors in predicting in-stent restenosis 6 months after PCI. 5

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“…11 In the case of DES implantation after predilatation, it was shown that if the DES did not cover the entire predilated segment, the edge area free of endothelial cells would be at risk of an edge effect caused by a increased neointimal thickness. 12 Lemos et al 13 confirmed that edge restenosis was associated with balloon trauma outside the stented segment.…”

Section: Discussionmentioning

confidence: 99%

Drug-Eluting Stents in Bifurcations

Guérin

Pilet

Finet

et al. 2010

Circ: Cardiovascular Interventions

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Background-The use of a drug-eluting stent (DES) has strongly limited the incidence of in-stent restenosis in bifurcation lesions; nevertheless, restenosis still remains a problem at the origin of the bifurcation side branch. The aim of this study is to analyze the consequences of the kissing postdilatation technique on 5 DESs, using microfocus x-ray computerized tomography and scanning electron microscopy. Methods and Results-Five different DESs (Cypher, Cypher Select, Endeavor, Taxus Express, and Taxus Liberté) were deployed using kissing postdilatation protocols in a bench-top model. For all types of DES, microfocus x-ray computerized tomography analysis showed that (1) kissing postdilatation of the stent by 2 coaxial balloons caused elliptic deformation in the proximal segment and (2) kissing postdilatation technique reduced the ratio of potential metal to artery (manufacturer's data/calculated ratio [%]: Cypher, 12.7/8.8; Cypher Select, 13.5/10.2; Endeavor, 19.0/13.3; Taxus Express, 20.5/4.7; Taxus Liberté, 17.9/12.5) and the potential drug application to area in the proximal segment, including the ostial struts (struts adjacent to and lying around the side branch ostium) (manufacturer's data/calculated drug application [g/mm 2 ]: Cypher, 1.4/1.0; Cypher Select, 1.4/1.1; Endeavor, 1.6/1.1; Taxus Express, 1.0/0.7; Taxus Liberté, 1.0/0.7). Scanning electron microscopy analysis showed a significantly greater coating damage to the ostial struts in all stents evaluated (PϽ0.05). Conclusions-Commercially available DESs subjected to simultaneous kissing balloon postdilatation in an unconstrainedmodel may contribute to side branch ostial restenosis by proximal segment elliptic deformation and damage to the polymer coating. (Circ Cardiovasc Interv. 2010;3:120-126.)Key Words: bifurcations Ⅲ stents Ⅲ angioplasty Ⅲ coronary disease Ⅲ restenosis B ifurcation lesions frequently occur in Ϸ15% of percutaneous coronary interventions. 1,2 Angioplasty with baremetal coronary stenting became the routine treatment for these lesions, but bifurcation stenting was still associated with a high rate of restenosis, especially when multiple stents were used. 2,3 The use of a drug-eluting stent (DES) has been reported to reduce restenosis in bifurcation lesions; however, side branch (SB) ostial restenosis still remains a problem in 10% to 20% of cases. 4 -7 Implanting a second stent in the SB does not limit restenosis, 6 and systematic SB stenting seems to be associated with a higher risk of restenosis than with the provisional T-stenting technique. 6,8 The high rate of SB ostium restenosis could be due to limited strut coverage in this area, with consequently inadequate drug distribution to the stented artery. 9 The aim of this study was to analyze the consequences of the kissing postdilatation technique (postdilatation by using simultaneous kissing balloon inflation) on 5 DESs commercially available in France, using microfocus x-ray computerized tomography (MFCT) and scanning electron microscopy (SEM). Clinical Perspective on p 126 M...

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Neointimal Hyperplasia after Stenting in a Human Mammary Artery Organ Culture

Cited by 21 publications

References 24 publications

Stent Implantation Activates RhoA in Human Arteries: Inhibitory Effect of Rapamycin

Stent Implantation Activates RhoA in Human Arteries: Inhibitory Effect of Rapamycin

Leukotriene Receptor Antagonism and the Prevention of Extracellular Matrix Degradation During Atherosclerosis and In-Stent Stenosis

Drug-Eluting Stents in Bifurcations

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