Vein quality influences neointimal hyperplasia in an organ culture model of human saphenous vein

Wilson, Y.G.; Davies, AH; Southgate, KM; Currie, I.C.; Sheffield, E.; Baird, RN; Lamont, PM; Angelini, Gianni D

doi:10.1016/s1078-5884(97)80064-0

Cited by 16 publications

(17 citation statements)

References 26 publications

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“…As published previously, 31 a high proportion of saphenous veins used for coronary artery bypass grafting have a preexisting thickening. VSMCs in these thickenings are longitudinally orientated, in contrast to the circumferentially orientated medial VSMCs.…”

Section: Resultsmentioning

confidence: 58%

Injury Induces Dedifferentiation of Smooth Muscle Cells and Increased Matrix-Degrading Metalloproteinase Activity in Human Saphenous Vein

Johnson

Eys

Angelini

et al. 2001

ATVB

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Abstract-Long-term patency of human saphenous vein bypass grafts is low because of intimal thickening and superimposed atherosclerosis. Matrix-degrading metalloproteinases (MMPs) and changes in vascular smooth muscle cell (VSMC) phenotype are thought to be essential for the VSMC migration that contributes to intimal thickening. We examined VSMC phenotype and MMP activity in saphenous veins obtained before and after surgical manipulation. Surgical preparation of the veins significantly increased pro-MMP-1 expression by 2-fold and significantly reduced tissue inhibitor of MMPs (TIMP)-2 expression, whereas MMP-3 and TIMP-1 were unaffected. Furthermore, caseinolytic and gelatinolytic activities measured by in situ zymography were dramatically elevated by injury. The expression of desmin and smoothelin was significantly decreased by injury, whereas vimentin expression was significantly increased. In addition, these changes in phenotype and MMP activity were localized to a subpopulation of VSMCs, the circumferential medial VSMCs. Our data show that surgical preparative injury induces phenotypic modulation of a subpopulation of medial VSMCs to a synthetic phenotype and increases MMP activity. This may favor matrix degradation, VSMC migration, and the subsequent intimal thickening that leads to graft failure. Medial VSMCs exist in the normal blood vessel wall in the contractile (differentiated) phenotype. These have a "spindlelike" morphology, maintain vessel wall tone, and are rich in contractile and intermediate filament proteins (IFPs). It has been suggested that migrating and proliferating VSMCs have dedifferentiated to a synthetic phenotype, characterized by a reduction in contractile proteins and alterations in IFPs (see review by Owens 5 ). Recent studies illustrate that the amounts of the IFPs vimentin and desmin, the cytoskeleton-related protein smoothelin, and the contractile proteins ␣-smooth muscle (SM) actin, SM myosin heavy chain (SMMHC), and tropomyosin change when VSMCs shift from the contractile to the synthetic phenotype. [5][6][7] Mechanical injury to the blood vessel wall, particularly endothelial damage, is thought to trigger phenotypic modulation of medial VSMCs, shifting them toward the synthetic phenotype (see reviews by Thyberg and colleagues 8 -10 ). To enable VSMC migration, remodeling of the basement membrane and of the interstitial collagenous matrix that maintains VSMCs in a quiescent state must occur. 11 Mechanical injury of aortic explants 12 and isolated VSMCs 13 stimulates the production of extracellular matrix-degrading metalloproteinases (MMPs), which are mainly associated with VSMCs of the synthetic phenotype. 14,15 Injury of rat carotid arteries 16 and human saphenous veins 17 increases the expression of basement membrane-degrading MMP-2 and MMP-9. Furthermore, MMP inhibitors,12,[18][19][20] as well as gene transfer of the endogenous tissue inhibitors of MMPs (TIMPs), [21][22][23][24][25] have demonstrated the involvement of MMPs in injury-stimulated intimal thickening. Injury also...

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Section: Resultsmentioning

confidence: 58%

Injury Induces Dedifferentiation of Smooth Muscle Cells and Increased Matrix-Degrading Metalloproteinase Activity in Human Saphenous Vein

Johnson

Eys

Angelini

et al. 2001

ATVB

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“…However, most of the experiments dealing with assessment of IH development were performed using either cultured endothelial cell lines or nonperfused ex vivo venous segments [9,13,[15][16][17][22][23][24]. Since low sheer stress may be one of the major stimuli leading to IH development [10,25], ex vivo perfusion is advantageous in order to test modulations of hemodynamics, anastomosis configuration and graft design with respect to IH development under standardized conditions.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Morphological and Functional Alterations of Human Saphenous Veins after Seven and Fourteen Days of ex vivo Perfusion

Paroz

Probst²,

Saucy³

et al. 2004

Eur Surg Res

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Intimal hyperplasia (IH) is a vessel wall remodeling process responsible of early failure after vascular surgery or endovascular interventions. An ex vivo perfusion was used to study human venous segments regarding functional, histomorphological, immunohistochemical and molecular alterations after 7 (group 1, n = 6) and 14 days (group 2, n = 6) of ex vivo perfusion. All vessel segments showed preserved smooth muscle function before and after perfusion. Histomorphometry revealed IH development which was more pronounced after 14 days rather than 7 days (p < 0.05). Expression of CD34, factor VIII, α-actin and MIB-1 was demonstrated in all segments from both groups indicating that muscular and endothelial integrity was preserved after ex vivo perfusion of up to 14 days. PAI-1 mRNA expression was significantly increased after perfusion (p < 0.05), suggesting that the endothelial fibrinolytic function may be modulated in this ex vivo perfusion model of human saphenous veins.

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“…Davies et al [123] and Wilson et al [124] have shown diffuse changes in intimal hyperplasia and muscular hypertrophy in saphenous and cephalic veins prior to their use in bypass surgery, suggesting that pre-existing disease may predispose vein grafts to stenosis due to inherent susceptibility of diseased veins to intimal hyperplasia.…”

Section: Alterations In Gene Expression With Stretch: Similarities Wimentioning

confidence: 99%

The Effect of Pressure-Induced Mechanical Stretch on Vascular Wall Differential Gene Expression

et al. 2012

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High blood pressure is responsible for the modulation of blood vessel morphology and function. Arterial hypertension is considered to play a significant role in atherosclerotic ischaemic heart disease, stroke and hypertensive nephropathy, whereas high venous pressure causes varicose vein formation and chronic venous insufficiency and contributes to vein bypass graft failure. Hypertension exerts differing injurious forces on the vessel wall, namely shear stress and circumferential stretch. Morphological and molecular changes in blood vessels ascribed to elevated pressure consist of endothelial damage, neointima formation, activation of inflammatory cascades, hypertrophy, migration and phenotypic changes in vascular smooth muscle cells, as well as extracellular matrix imbalances. Differential expression of genes encoding relevant factors including vascular endothelial growth factor, endothelin-1, interleukin-6, vascular cell adhesion molecule, intercellular adhesion molecule, matrix metalloproteinase-2 and -9 and plasminogen activator inhibitor-1 has been explored using ex vivo cellular or organ stretch models and in vivo experimental animal models. Identification of pertinent genes may unravel new therapeutic strategies to counter the effects of pressure-induced stretch on the vessel wall and hence minimise its notable complications.

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Vein quality influences neointimal hyperplasia in an organ culture model of human saphenous vein

Abstract: Pre-existing vein quality as measured by PIT correlates with the development of neointimal hyperplasia in culture, adding further support to clinical evidence that poor vein quality predisposes to vein graft stenosis due to an inherent susceptibility to intimal hyperplasia.

Cited by 16 publications

References 26 publications

Injury Induces Dedifferentiation of Smooth Muscle Cells and Increased Matrix-Degrading Metalloproteinase Activity in Human Saphenous Vein

Injury Induces Dedifferentiation of Smooth Muscle Cells and Increased Matrix-Degrading Metalloproteinase Activity in Human Saphenous Vein

Comparison of Morphological and Functional Alterations of Human Saphenous Veins after Seven and Fourteen Days of ex vivo Perfusion

The Effect of Pressure-Induced Mechanical Stretch on Vascular Wall Differential Gene Expression

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