Homocysteine from endothelial cells promotes LDL nitration and scavenger receptor uptake

Griffiths, Helen R.; Aldred, Sarah; Dale, Chloe; Nakano, Emi; Kitas, George D.; Grant, Melissa M.; Nugent, Daniel; Taiwo, Fatai A.; Li, Li; Powers, Hilary J.

doi:10.1016/j.freeradbiomed.2005.08.039

Cited by 32 publications

(26 citation statements)

References 40 publications

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“…Early scepticism that the increased prevalence of vascular disease in RA patients could be attributed to high dose steroid therapy has not been discounted and the involvement of the chronic systemic inflammatory response in causing accelerated atherosclerosis has been implicated. The presence of elevated levels of modified LDL in the plasma of RA patients, a putative biomarker of atherosclerotic risk, further supports the role of ROS=RNS-mediated processes in the vascular complications of RA (94,95). Previous reports have also shown increased circulating levels of autoantibodies against modified LDL in RA, suggesting an antigenic role for modified LDL in stimulating autoantibody formation (94,172).…”

Section: E Managing Vascular Complications In Rasupporting

confidence: 58%

“…Autoantibody titers against oxidized LDL are elevated in early RA patients compared to Malondialdehyde, nitration healthy controls (61). We have also observed increased levels of autoantibodies towards nitrated LDL in RA patients with cardiovascular complications, where nitrated LDL was more avidly scavenged by macrophages than native or oxidized LDL (95). These data represent an association between protein modification and change of function but do not imply causality; indeed recent studies have shown that myeloperoxidase-catalyzed LDL-phospholipid oxidation can elicit a proinflammatory phenotype on aortic endothelial cells (53).…”

Section: Amino Acid Oxidation Chemistry and Its Relevance To Automentioning

confidence: 51%

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Aberrant Reactive Oxygen and Nitrogen Species Generation in Rheumatoid Arthritis (RA): Causes and Consequences for Immune Function, Cell Survival, and Therapeutic Intervention

Phillips

Dias

Kitas

et al. 2010

Antioxidants & Redox Signaling

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The infiltration and persistence of hematopoietic immune cells within the rheumatoid arthritis (RA) joint results in elevated levels of pro-inflammatory cytokines, increased reactive oxygen (ROS) and -nitrogen (RNS) species generation, that feeds a continuous self-perpetuating cycle of inflammation and destruction. Meanwhile, the controlled production of ROS is required for signaling within the normal physiological reaction to perceived "foreign matter" and for effective apoptosis. This review focuses on the signaling pathways responsible for the induction of the normal immune response and the contribution of ROS to this process. Evidence for defects in the ability of immune cells in RA to regulate the generation of ROS and the consequence for their immune function and for RA progression is considered. As the hypercellularity of the rheumatoid joint and the associated persistence of hematopoietic cells within the rheumatoid joint are symptomatic of unresponsiveness to apoptotic stimuli, the role of apoptotic signaling proteins (specifically Bcl-2 family members and the tumor suppressor p53) as regulators of ROS generation and apoptosis are considered, evaluating evidence for their aberrant expression and function in RA. We postulate that ROS generation is required for effective therapeutic intervention.

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Section: E Managing Vascular Complications In Rasupporting

confidence: 58%

Section: Amino Acid Oxidation Chemistry and Its Relevance To Automentioning

confidence: 51%

Aberrant Reactive Oxygen and Nitrogen Species Generation in Rheumatoid Arthritis (RA): Causes and Consequences for Immune Function, Cell Survival, and Therapeutic Intervention

Phillips

Dias

Kitas

et al. 2010

Antioxidants & Redox Signaling

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“…Oxidized LDL uptake by U937 monocytes LDL was isolated from healthy donors by gradient ultracentrifugation, minimally oxidized with copper, and then labeled with 1,1 0 -dioctadecyl-3,3,3 0 ,3 0 -tetramethylindocarbocyanine perchlorate (DiI; Molecular Probes) as described previously [25]. DiIlabeled oxidized LDL (10 mg/well) was incubated with U937 cells (1 Â 10 6 /ml), which had been treated with free FA or BSA as control, for 16 h at 37 1C.…”

Section: Monocyte Adhesion To Rat Aortamentioning

confidence: 99%

Palmitate promotes monocyte atherogenicity via de novo ceramide synthesis

Gao

Pararasa

Dunston

et al. 2012

Free Radical Biology and Medicine

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“…However, other case-control studies have not demonstrated such a causal association, and the mechanism of Hcy-induced AS remains to be fully elucidated (29,30). In addition, whether Hcy itself is a major factor or an indirect metabolic marker of certain biochemical processes, which occur in AS is unclear.…”

Section: Discussionmentioning

confidence: 99%

Ratio of S-adenosylmethionine to S-adenosylhomocysteine as a sensitive indicator of atherosclerosis

Zhang

Liu

et al. 2016

Mol Med Report

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Abstract. The present study aimed to confirm whether the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) is a sensitive indicator, and whether it can be used as a biomarker for the clinical diagnosis of atherosclerosis. Apolipoprotein E (ApoE) -/-mice were randomly divided into four groups and fed with a high methionine diet for 15 weeks. Serum levels of homocysteine (Hcy) were measured using an automatic biochemistry analyzer. The concentrations of SAM and SAH were determined using high-performance liquid chromatography. The methylation levels of B1 repetitive elements, adipocyte fatty acid binding protein (FABP4), monocyte chemoattractant protein-1 (MCP-1) and extracellular superoxide dismutase (EC-SOD) were analyzed using nested touchdown-methylation-specific-polymerase chain reaction analysis. After 15 weeks, compared with the normal control group, serum concentrations of Hcy were significantly increased by 1.15-, 2.54-and 1.17-fold (P<0.05) in the ApoE -/-control group, Meth group and Meth-F group, respectively. The sizes of the atherosclerotic lesions were increased in the ApoE -/-control group, Meth group and Meth-F group, by up to 1.44-, 2.40-and 1.45-fold, respectively, compared with the normal control group (P<0.05). The concentrations of SAM were significantly increased by 3.02-, 3.42-and 2.46-fold in the ApoE -/-control group, Meth group and Meth-F group, respectively (P<0.05). The ratios of SAM/SAH were increased by 1.67-and 2.75-fold in the in ApoE -/-control group and Meth group, respectively, compared with the normal control group. The methylation levels of B1 repetitive elements, FABP4, MCP-1 and EC-SOD were decreased and exhibited hypomethylation. The methylation statuses of these genes were correlated with the ratio of the serum levels of SAM and SAH. These findings suggested that the SAM/SAH ratio is a biomarker and may provide a sensitive indicator for the clinical diagnosis of atherosclerosis.

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Homocysteine from endothelial cells promotes LDL nitration and scavenger receptor uptake

Cited by 32 publications

References 40 publications

Aberrant Reactive Oxygen and Nitrogen Species Generation in Rheumatoid Arthritis (RA): Causes and Consequences for Immune Function, Cell Survival, and Therapeutic Intervention

Aberrant Reactive Oxygen and Nitrogen Species Generation in Rheumatoid Arthritis (RA): Causes and Consequences for Immune Function, Cell Survival, and Therapeutic Intervention

Palmitate promotes monocyte atherogenicity via de novo ceramide synthesis

Ratio of S-adenosylmethionine to S-adenosylhomocysteine as a sensitive indicator of atherosclerosis

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