Superoxide-mediated modification of low density lipoprotein by arterial smooth muscle cells.

Heinecke, Jay W.; Baker, L.; Rosen, Henry; Chait, Alan

doi:10.1172/jci112371

Cited by 613 publications

(343 citation statements)

References 23 publications

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“…1 " 5 -7 -9 - 15 Certain of these pathways may generate particulate lipoprotein. For example, bifunctional aldehydes formed during lipid peroxidation 35 -36 could crosslink LDL in the intima of the arterial wall.…”

Section: Discussionmentioning

confidence: 99%

Phagocytosis of lipase-aggregated low density lipoprotein promotes macrophage foam cell formation. Sequential morphological and biochemical events.

Heinecke

Suits

Aviram

et al. 1991

Arterioscler Thromb

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Macrophages internalize aggregated low density lipoprotein (LDL) byReceived January 22, 1990; revision accepted July 13, 1991. (LDL) by the LDL receptor. 2 When excess cholesterol accumulates, cholesterol synthesis is repressed and the number of LDL receptors is downregulated, thereby decreasing the internalization of LDL. Because LDL receptor activity is tightly coupled to the amount of free cholesterol in cells, it is likely that a pathway distinct from LDL receptor-mediated endocytosis is responsible for the pathological accumulation of cholesterol. 1 -2 Apolipoprotein B-100 is the ligand for the binding of LDL to its receptor. 2 When the lysine residues of apolipoprotein B-100 are acetylated, LDL receptor recognition is lost. 1 -3 Macrophages possess another cell-surface receptor, the scavenger receptor, that binds and internalizes altered forms of LDL, including acetylated LDL, malondialdehyde-modified LDL, and oxidized LDL. 1 -3 -5 -7 In contrast to the LDL Downloaded from http://ahajournals.org by on April 3, 2019

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Section: Discussionmentioning

confidence: 99%

Phagocytosis of lipase-aggregated low density lipoprotein promotes macrophage foam cell formation. Sequential morphological and biochemical events.

Heinecke

Suits

Aviram

et al. 1991

Arterioscler Thromb

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“…As described previously, LDL was isolated from the plasma of normal human volunteers by preparative ultracentrifugation, and purified by sequential density gradient ultracentrifugation [26,27]. LDL was stored under nitrogen in the dark at 4°C with 1 mmol/l EDTA.…”

Section: Methodsmentioning

confidence: 99%

Thiazolidinediones reduce the LDL binding affinity of non-human primate vascular cell proteoglycans

et al. 2004

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Aims/hypothesis. Retention of atherogenic lipoproteins in the artery wall by proteoglycans is a key step in the development of atherosclerosis. Thiazolidinediones have been shown to reduce atherosclerosis in mouse models. The aim of this study was to determine whether thiazolidinediones modify vascular proteoglycan synthesis in a way that decreases LDL binding. Methods. Primate aortic smooth muscle cells were exposed to troglitazone or rosiglitazone, or no stimulus at all for a 24-hour steady-state labelling period. Sulphate incorporation, size and LDL binding affinity of proteoglycans were determined. Proteoglycans secreted by cells in the presence or absence of troglitazone were separated into large and small classes by size exclusion chromatography, and LDL binding affinity was determined. Results. Proteoglycans synthesised by cells exposed to troglitazone or rosiglitazone were smaller, with decreased sulphate incorporation and decreased LDL binding affinity. However, troglitazone had a greater effect than rosiglitazone. Troglitazone reduced the LDL binding affinities of both the large and small proteoglycans compared with control. The binding differences persisted when glycosaminoglycan chains released from proteoglycans were incubated with LDL, indicating that troglitazone affects the glycosaminoglycan synthetic machinery of these cells. Conclusions/interpretation. Thiazolidinediones decrease the LDL binding affinity of the proteoglycans synthesised by primate aortic smooth muscle cells. This could, in part, account for the reduced atherosclerosis observed in animal models.

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“…[67][68][69] Superoxide is believed to react with endothelial nitric oxide to yield peroxynitrite, thereby limiting the normal vasodilation response. 70,71 Both superoxide and peroxynitrite contribute to the modification of tissues, resulting in the generation of lipid peroxides and in the case of peroxynitrite, the modification of proteins by tyrosine nitration and the formation of 3-nitrotyrosine. The recent findings that heme oxygenase-1 (HO-1) and glutathione peroxidase (GPx) expression and activity are impaired in cultured vascular endothelial cells treated with homocysteine suggest that HHcy can inhibit the antioxidant potential of cells.…”

Section: Oxidative Stressmentioning

confidence: 99%

Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease

2004

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Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease, including ischemic heart disease, stroke, and peripheral vascular disease. Mutations in the enzymes responsible for homocysteine metabolism, particularly cystathionine b-synthase (CBS) or 5,10-methylenetetrahydrofolate reductase (MTHFR), result in severe forms of HHcy. Additionally, nutritional deficiencies in B vitamin cofactors required for homocysteine metabolism, including folic acid, vitamin B6 (pyridoxal phosphate), and/or B12 (methylcobalamin), can induce HHcy. Studies using animal models of genetic-and diet-induced HHcy have recently demonstrated a causal relationship between HHcy, endothelial dysfunction, and accelerated atherosclerosis. Dietary enrichment in B vitamins attenuates these adverse effects of HHcy. Although oxidative stress and activation of proinflammatory factors have been proposed to explain the atherogenic effects of HHcy, recent in vitro and in vivo studies demonstrate that HHcy induces endoplasmic reticulum (ER) stress, leading to activation of the unfolded protein response (UPR). This review summarizes the current role of HHcy in endothelial dysfunction and explores the cellular mechanisms, including ER stress, that contribute to atherothrombosis.

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Superoxide-mediated modification of low density lipoprotein by arterial smooth muscle cells.

Cited by 613 publications

References 23 publications

Phagocytosis of lipase-aggregated low density lipoprotein promotes macrophage foam cell formation. Sequential morphological and biochemical events.

Phagocytosis of lipase-aggregated low density lipoprotein promotes macrophage foam cell formation. Sequential morphological and biochemical events.

Thiazolidinediones reduce the LDL binding affinity of non-human primate vascular cell proteoglycans

Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease

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