Reduction of Lipid Peroxidation with Intraoperative Superoxide Dismutase Treatment Decreases Intimal Hyperplasia in Experimental Vein Grafts

Huynh, Thi Thanh Tam; Trovato, Matthew J.; Barber, Lizzie; Safi, Hazim J.; Hagen, Per Otto

doi:10.1006/jsre.1999.5647

Cited by 28 publications

(15 citation statements)

References 35 publications

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“…[22][23][24][25] In fact, focal vascular trauma has been shown to upregulate ⅐O 2 Ϫ in the arterial system, 26,27 although studies of vascular grafts have been limited. 28 Numerous growth factors released at the site of tissue injury, including thrombin, are known to increase NAD(P)H oxidase activity. 29 As shown in the present study, an inhibitor of NAD(P)H oxidase almost entirely abolished ⅐O 2 Ϫ production in SVGs.…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress and Lipid Retention in Vascular Grafts

et al. 2001

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Background-Because saphenous vein grafts (SVGs) exhibit greater cellular heterogeneity and worse clinical outcomes than arterial grafts (AGs), we examined oxidative stress and lipid retention in different vascular conduits. Methods and Results-In a porcine model of graft interposition into carotid artery, superoxide anion (⅐O 2 Ϫ ) was measured at 2 weeks after surgery. SVGs demonstrated increased ⅐O 2 Ϫ production compared with AGs (SOD-inhibitable nitro blue tetrazolium reduction, PϽ0.01). The NAD(P)H oxidase inhibitor diphenyleneiodonium (PϽ0.01) abolished SVGderived ⅐O 2 Ϫ , whereas the inhibitors of other pro-oxidant enzymes were ineffective. The change in oxidative stress was also reflected by lower activity of the endogenous antioxidant superoxide dismutase in SVGs than in AGs (PϽ0.001). SVG remodeling was associated with increased synthesis of sulfated glycosaminoglycans and augmented expression of a core protein, versican. These changes were accompanied by SVGs retaining significantly more 125 I-labeled LDL than AGs ex vivo (PϽ0.001). In hyperlipemic animals, lipid accumulation and oxidized epitopes were preferentially noted in the intima of SVGs at 1 month after surgery. Conclusions-This study demonstrated significant differences in the biology of SVGs and AGs. SVGs exhibited higher oxidative stress, LDL accumulation, and the presence of oxidized epitopes. These findings suggest that proatherogenic changes in SVGs may commence early after surgical revascularization.

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Section: Discussionmentioning

confidence: 99%

Oxidative Stress and Lipid Retention in Vascular Grafts

et al. 2001

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“…14,15 Free oxygen radicals play a role in the etiology of the intimal hyperplasia as reported previously. 5,7 In one of those studies, Huynh et al interposed a venous graft into rabbit carotid artery and administered intraoperative local polyethylene glycol superoxide dismutase as antioxidant therapy, which ultimately reduced the intimal thickening. 7 Many studies discovered the positive effect of ascorbate on endothelial functions due to its potent antioxidant effect.…”

Section: Discussionmentioning

confidence: 99%

“…5,7 In one of those studies, Huynh et al interposed a venous graft into rabbit carotid artery and administered intraoperative local polyethylene glycol superoxide dismutase as antioxidant therapy, which ultimately reduced the intimal thickening. 7 Many studies discovered the positive effect of ascorbate on endothelial functions due to its potent antioxidant effect. 16,17 Although vitamin C generally has an antioxidant effect, it may act as a pro-oxidant by converting the free radicals to hydrogen peroxide.…”

Section: Discussionmentioning

confidence: 99%

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The Effect of Ascorbic Acid on Proliferation of Vascular Smooth Muscle Cells and Intimal Hyperplasia

Gokalp¹,

Yurekli²,

Mavioğlu³

et al. 2013

Turkiye Klinikleri J Med Sci

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A AB BS ST TR RA AC CT T O Ob bj je ec ct ti iv ve e: : Proliferation of smooth muscle cells leading to intimal hyperplasia developing at vascular intervention sites plays a major role in the development of restenosis. Ascorbic acid is a potent anti-oxidant with antiproliferative properties. The aim of this study was to investigate such effect of ascorbic acid on intimal hyperplasia. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : Twenty-one male white New Zealand rabbits weighing 2-3 kg were selected. The animals were allocated to three groups each consisting of seven rabbits. Group 1 was the sham group. Group 2 was the control group and Group 3 consisted of rabbits receiving ascorbic acid. The right carotid arteries of the subjects in Groups 2 and 3 were transected and re-anastomosed. A daily dose of 100 mg ascorbic acid per kg body weight was administered intraperitoneally for 14 days to rabbits in Group 3. Rabbits in Group 2 were not subject to any pharmaceutical agent. All the subjects were sacrificed at the end of postoperative day 28. Their right carotid arteries were resected and were subject to histopathologic examination for smooth muscle cell proliferation and intimal hyperplasia. The arterial segments were fixed in 10% buffered formalin solution until the time of histological analysis. Each vessel was sectioned serially in 2-mm increments from the prepared paraffin blocks. Sections of 5 µm thickness were stained with hematoxylin and eosin (H&E) and Masson Trichrome. The diameters of vessels and their luminal areas, and the areas of tunica intima and tunica media were measured with 10X magnification. The thicknesses of tunica intima and tunica media were measured with 20X magnification. The morphometric measurements were then compared between groups. R Re es su ul lt ts s: : Intimal thickness and intimal area were significantly lower in Group 1 when compared with the other groups (p=0.004, p=0.003). In Group 3, the ratios of tunica intima thickness/tunica media thickness and area of tunica intima/area of tunica media were significantly lower than those of Group 2 (p=0.015, p=0.046). C Co on nc cl lu us si io on n: : Ascorbic acid reduces the intimal hyperplasia developing after vascular anastomoses. K Ke ey y W Wo or rd ds s: : Ascorbic acid; muscle, smooth; hyperplasia Ö ÖZ ZE ET T A Am ma aç ç: : Düz kas hücre proliferasyonu ve bunun ardından gelişen intimal hiperplazi, vasküler girişimden sonra meydana gelen restenozda önemli rol alır. Askorbik asit antiproliferatif özelliği olan güçlü bir antioksidandır. Bu çalışmanın amacı, askorbik asidin bu etkilerinden yola çıkarak intimal hiperplazi üzerindeki etkisini incelemektir. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Rastgele seçilen 21 adet ortalama 2-3 kg ağırlığında Yeni Zelanda tipi erkek tavşan, her birinde 7 tavşan bulunan 3 gruba ayrıldı. Birinci gruba (Grup 1) hiç-bir girişim yapılmadı. İkinci gruba (Grup 2) anastomoz yapıldı, ancak hiçbir ilaç verilmedi. Üçüncü gruba (Gup 3) ise anstomoz yapılıp askorbik asit verildi. G...

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“…These differences in ROS processing may contribute to the increased patency of arterial grafts. Intraoperative PEG-SOD treatment in a rabbit jugular-carotid interposition model reduced the I/M ratio and increased luminal area of the graft at 28 days, but no improvement in vasomotor function was observed 107 . Intraoperative delivery of adenovirus encoding extracellular-SOD (AdEC-SOD) reduced macrophage accumulation but not I/M ratio or BrdU incorporation at 4 weeks in a rabbit model 108 .…”

Section: Endothelial Injury and Loss Of Endothelial Vasoprotective Famentioning

confidence: 92%

Gene Therapy for the Prevention of Vein Graft Disease

Mueller

Kontos

2015

Translating Gene Therapy to the Clinic

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Ischemic cardiovascular disease remains the leading cause of death worldwide. Despite advances in the medical management of atherosclerosis over the past several decades, many patients require arterial revascularization to reduce mortality and alleviate ischemic symptoms. Technological advancements have led to dramatic increases in the use of percutaneous and endovascular approaches, yet surgical revascularization (bypass surgery) with autologous vein grafts remains a mainstay of therapy for both coronary and peripheral artery disease. Although bypass surgery is highly efficacious in the short-term, long-term outcomes are limited by relatively high failure rates as a result of intimal hyperplasia, which is a common feature of vein graft disease.

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Reduction of Lipid Peroxidation with Intraoperative Superoxide Dismutase Treatment Decreases Intimal Hyperplasia in Experimental Vein Grafts

Cited by 28 publications

References 35 publications

Oxidative Stress and Lipid Retention in Vascular Grafts

Oxidative Stress and Lipid Retention in Vascular Grafts

The Effect of Ascorbic Acid on Proliferation of Vascular Smooth Muscle Cells and Intimal Hyperplasia

Gene Therapy for the Prevention of Vein Graft Disease

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