A surgical preparative technique for coronary bypass grafts of human saphenous vein which preserves medial and endothelial functional integrity

Angelini, Gianni D; Breckenridge, I. M.; Williams, Helen M.; Newby, Andrew C.

doi:10.1016/s0022-5223(19)36253-1

Cited by 38 publications

(16 citation statements)

References 15 publications

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“…Since endothelial cell coverage of the vein graft is vital for the success of the vein graft, 27 we examined whether inhibition of N-cadherin affects endothelial cell coverage. Interestingly, we observed that endothelial cell coverage was enhanced in vein segments expressing dn-N-cadherin.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of N-cadherin retards smooth muscle cell migration and intimal thickening via induction of apoptosis

Lyon

Koutsouki

Aguilera

et al. 2010

Journal of Vascular Surgery

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ObjectivesInhibition of vascular smooth muscle cell (VSMC) migration is a potential strategy for reducing intimal thickening during in-stent restenosis and vein graft failure. In this study, we examined the effect of disrupting the function of the VSMC adhesion molecule, N-cadherin, using antagonists, neutralizing antibodies, and a dominant negative, on VSMC migration and intimal thickening. Migration was assessed by the scratch-wound assay of human saphenous vein VSMCs and in a human saphenous vein ex vivo organ culture model of intimal thickening.ResultsInhibition of cadherin function using a pan-cadherin antagonist, significantly reduced migration by 53% ± 8% compared with the control peptide (n = 3; P < .05). Furthermore, inhibition of N-cadherin function with an N-cadherin antagonist, neutralizing antibodies, and adenoviral expression of dominant negative N-cadherin (RAd dn-N-cadherin), significantly reduced migration by 31% ± 2%, 23% ± 1% and 32% ± 7% compared with controls, respectively (n = 3; P < .05). Inhibition of cadherin function significantly increased apoptosis by between 1.5- and 3.3-fold at the wound edge. In an ex vivo model of intimal thickening, inhibition of N-cadherin function by infection of human saphenous vein segments with RAd dn-N-cadherin significantly reduced VSMC migration by 55% and increased VSMC apoptosis by 2.7-fold. As a result, intimal thickening was significantly suppressed by 54% ± 14%. Importantly, there was no detrimental effect of dn-N-cadherin on endothelial coverage; in fact, it was significantly increased, as was survival of cultured human saphenous vein endothelial cells.ConclusionsUnder the condition of this study, cell-cell adhesion mediated by N-cadherin regulates VSMC migration via modulation of viability. Interestingly, inhibition of N-cadherin function significantly retards intimal thickening via inhibition of VSMC migration and promotion of endothelial cell survival. We suggest that disruption of N-cadherin-mediated cell-cell contacts is a potential strategy for reducing VSMC migration and intimal thickening.

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Section: Discussionmentioning

confidence: 99%

Inhibition of N-cadherin retards smooth muscle cell migration and intimal thickening via induction of apoptosis

Lyon

Koutsouki

Aguilera

et al. 2010

Journal of Vascular Surgery

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“…For example, Gottlob [8] proposed a somewhat complicated atraumatic ‘dissection without touching’ technique in which ‘The venous graft is fixed by holding sutures to a bent rod of rubber’ to minimize handling. Other techniques also emphasize the need to reduce trauma and to preserve medial and endothelial integrity [9,10]. The potential benefit of providing mechanical support to the vein has been studied where a perivenous mesh prosthesis improves endothelial integrity and lumen diameter in a sheep vein graft model, with beneficial effects also being achieved in a small number of patients undergoing CABG [11].…”

Section: The Saphenous Vein As a Bypass Conduitmentioning

confidence: 99%

Endothelin‐1 and vein graft occlusion in patients undergoing bypass surgery

Dashwood

2009

Eur J Clin Investigation

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The saphenous vein is the most commonly used graft for revascularization procedures in patients with coronary artery disease and critical limb ischaemia. However, the patency rate of this vessel is poor, with a high proportion of patients requiring further surgery. Early graft occlusion is caused by vasoconstriction or thrombus formation, with later stages of graft failure being due to neointimal formation or atherosclerosis. Apart from its potent constrictor action, endothelin-1 is also a potent proliferative and proinflammatory peptide that is implicated in a number of vascular diseases. The surgical trauma caused during preparation of the saphenous vein as a bypass graft stimulates the release of a number of factors affecting vascular reactivity and structure, including endothelin-1. Endothelin-1 not only constricts animal and human isolated saphenous vein segments but also causes vascular smooth muscle proliferation and neointimal thickening in vitro, actions that are mediated via endothelin (A and B) receptors. Experimentally, the effects of subtype-selective and dual receptor antagonists have been shown to inhibit endothelin-1-mediated constriction and cell proliferation of the saphenous vein. In this review, data supporting a role of endothelin-1 in vein graft occlusion are presented, and the therapeutic potential of endothelin receptor antagonists in improving graft performance is discussed.

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“…In veins distended with 100 mmHg, however, there was lifting and rounding of individual endothelial cells [86]. Consistent with disruption of the endothelium, distension of human SV with pressures greater than the patients' blood pressure decreased prostacyclin and NO release [89]. Given the role of the endothelium in regulating vasoactivity, maintaining a nonthrombogenic intima, and regulating SMC proliferation, its denudation or damage could be expected to promote thrombosis and intimal hyperplasia.…”

Section: Endotheliummentioning

confidence: 85%

Biomechanics and Mechanobiology of Saphenous Vein Grafts

Gooch

Firstenberg

Shrefler

et al. 2018

Journal of Biomechanical Engineering

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Within several weeks of use as coronary artery bypass grafts (CABG), saphenous veins (SV) exhibit significant intimal hyperplasia (IH). IH predisposes vessels to thrombosis and atherosclerosis, the two major modes of vein graft failure. The fact that SV do not develop significant IH in their native venous environment coupled with the rapidity with which they develop IH following grafting into the arterial circulation suggests that factors associated with the isolation and preparation of SV and/or differences between the venous and arterial environments contribute to disease progression. There is strong evidence suggesting that mechanical trauma associated with traditional techniques of SV preparation can significantly damage the vessel and might potentially reduce graft patency though modern surgical techniques reduces these injuries. In contrast, it seems possible that modern surgical technique, specifically endoscopic vein harvest, might introduce other mechanical trauma that could subtly injure the vein and perhaps contribute to the reduced patency observed in veins harvested using endoscopic techniques. Aspects of the arterial mechanical environment influence remodeling of SV grafted into the arterial circulation. Increased pressure likely leads to thickening of the medial wall but its role in IH is less clear. Changes in fluid flow, including increased average wall shear stress, may reduce IH while disturbed flow likely increase IH. Nonmechanical stimuli, such as exposure to arterial levels of oxygen, may also have a significant but not widely recognized role in IH. Several potentially promising approaches to alter the mechanical environment to improve graft patency are including extravascular supports or altered graft geometries are covered.

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A surgical preparative technique for coronary bypass grafts of human saphenous vein which preserves medial and endothelial functional integrity

Cited by 38 publications

References 15 publications

Inhibition of N-cadherin retards smooth muscle cell migration and intimal thickening via induction of apoptosis

Inhibition of N-cadherin retards smooth muscle cell migration and intimal thickening via induction of apoptosis

Endothelin‐1 and vein graft occlusion in patients undergoing bypass surgery

Biomechanics and Mechanobiology of Saphenous Vein Grafts

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