Mechanism of Dacron-activated monocytic cell oxidation of low density lipoprotein

Recent studies find that vitamin E is not efficacious in the secondary prevention of cardiovascular events, perhaps because vitamin E does not efficiently block oxidation pathways known to be operative in atherosclerotic arteries. "Non-antioxidant" properties of vitamin E, however, could be important in the primary prevention of atherosclerosis and its complications. Our in vitro studies show that alpha-tocopherol can preserve endothelial migration in the presence of cell-oxidized LDL. This effect might improve the healing of endothelial injuries at sites of arterial repair or angioplasties, especially in lipid-laden arterial walls.

Section: Methodsmentioning

confidence: 99%

α-tocopherol preserves endothelial cell migration in the presence of cell-oxidized low-density lipoprotein by inhibiting changes in cell membrane fluidity

Aalst

Burmeister

Fox

et al. 2004

“…4 Oxidatively modified lipids and lipoproteins may have a role in recurrent stenosis after angioplasty and vascular graft failure, because oxidized low-density lipoproteins (oxLDL) possess a number of properties that would adversely affect healing, including inhibition of endothelial cell migration. 5 We have shown that Dacron graft material activates monocytic cells to oxidize low-density lipoprotein (LDL), 6 and that cell-modified LDL inhibits endothelial cell migration. 7 The mechanism by which oxLDL inhibits endothelial cell migration is an area of active investigation.…”

mentioning

confidence: 99%

Role of reactive oxygen species in inhibition of endothelial cell migration by oxidized low-density lipoprotein

Aalst

Zhang²,

Miyazaki³

et al. 2004

Self Cite

OxLDL inhibits endothelial cell migration, and may impair healing of arterial injuries. The mechanism of oxidized LDL inhibition is not known. Our in vitro studies show that the inhibitory properties are related to production of reactive oxygen species. Superoxide dismutase or inhibitors of reduced nicotinamide adenine dinucleotide phosphate oxidase can preserve endothelial migration in the presence of oxLDL. This might improve the healing of endothelial injuries at sites of arterial repair or angioplasty, especially in lipid-laden arterial walls.

“…Lipid oxidation products, but not native lipids or lipoproteins, cause cellular dysfunction in vitro, including inhibition of EC migration,4 stimulation of SMC proliferation,5 and increased platelet-derived growth factor (PDGF) and collagen production by SMCs,6, 7 which could impair graft healing in vivo. Studies have confirmed that prosthetic graft material induces monocytes to oxidize low-density lipoprotein (LDL),8 and lipid oxidation products accumulate in vascular grafts in vivo 9. In a previous rabbit study, hypercholesterolemia impaired prosthetic graft healing and was associated with increased anastomotic IH and macrophage infiltration and decreased endothelialization of the graft 10.…”

Section: Introductionmentioning

confidence: 99%

Antioxidant therapy reverses impaired graft healing in hypercholesterolemic rabbits

Rosenbaum

Miyazaki

Colles

et al. 2010

Self Cite

Objective Limited endothelial cell (EC) coverage and anastomotic intimal hyperplasia contribute to thrombosis and failure of prosthetic grafts. Lipid accumulation and lipid oxidation are associated with decreased EC migration and intimal hyperplasia. The goal of this study was to assess the ability of antioxidants to improve graft healing in hypercholesterolemic animals. Methods Rabbits were placed in one of four groups: chow plus N-acetylcysteine (NAC), chow plus probucol, chow with 1% cholesterol plus NAC, or chow with 1% cholesterol plus probucol. After two weeks, 12 cm long, 4 mm internal diameter expanded polytetrafluoroethylene grafts were implanted in the abdominal aorta. Six weeks after implantation, the grafts were removed and analyzed for cholesterol content, EC coverage, anastomotic intimal thickness, and the cellular composition of the neointima. Plasma samples were obtained to assess systemic oxidative stress. The data was compared with previously reported data from animals on chow and chow with 1% cholesterol diets. Results Prosthetic grafts from rabbits on a chow with 1% cholesterol diet had significantly greater anastomotic intimal thickening and lower EC coverage than grafts from rabbits on a chow diet. In hypercholesterolemic rabbits, antioxidant therapy decreased global oxidative stress as evidenced by a 40% decrease in plasma thiobarbituric acid reactive substances. In rabbits on the chow with 1% cholesterol diet, NAC decreased intimal hyperplasia at the proximal anastomosis by 29% and significantly increased graft EC coverage from 46% to 71% (P = .03). Following a similar pattern, probucol decreased intimal hyperplasia by 43% and increased graft EC coverage to 53% in hypercholesterolemic rabbits. Conclusions Global oxidative stress and anastomotic intimal hyperplasia are increased and endothelialization of prosthetic grafts is significantly reduced in rabbits on a high cholesterol diet. Antioxidant treatment improves EC coverage and decreases intimal hyperplasia. Reducing oxidative stress may promote healing of prosthetic grafts. Clinical Relevance Hypercholesterolemia is associated with an increased inflammatory response, elevated oxidative stress, and increased intimal hyperplasia following stent or vein graft placement in animal models and in humans. Reduced endothelialization is seen following stent or graft placement in hypercholesterolemic animals, and reduced EC growth and patency of EC-seeded grafts is found in humans with elevated serum lipid levels. Our results suggest that antioxidants are effective in reducing this pathologic response and improving graft healing.