Increased susceptibility to oxidation of low‐density lipoproteins isolated from patients with systemic sclerosis

Bruckdorfer, K. Richard; Hillary, Janet B.; Bunce, Tim D; Vancheeswaran, Rama; Black, Carol M.

doi:10.1002/art.1780380807

Cited by 82 publications

(42 citation statements)

References 37 publications

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“…Thus, increased levels of malondialdehyde in the circulation, in settings of platelet activation, may arise as a consequence of platelet activation rather than lipid peroxidation. A recent study (27) found that low-density lipoproteins from patients with scleroderma were more susceptible to oxidation than were those from healthy controls. Those authors concluded that the findings supported the hypothesis that free radical damage is involved in the development of scleroderma, and they suggested that direct measurement of oxidative stress in scleroderma would be of interest.…”

Section: Discussionmentioning

confidence: 98%

Evidence of free radical–mediated injury (isoprostane overproduction) in scleroderma

Stein

Tanner

Awad

et al. 1996

Arthritis & Rheumatism

154

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Objective. Free radical–induced oxidative stress with consequent lipid peroxidation and resultant tissue damage has been suggested as a potential mechanism of the pathogenesis of scleroderma. However, because reliable measurement of lipid peroxidation in vivo is difficult, it has not been possible to adequately examine this hypothesis. We have previously described a series of bioactive prostaglandin F2–like compounds, termed F2‐isoprostanes, produced in vivo in humans by the noncyclooxygenase, free radical–catalyzed, peroxidation of arachidonic acid and have shown them to be a reliable measure of lipid peroxidation in vivo. In the present study, we determined whether scleroderma is associated with enhanced oxidative stress.Methods. As a measure of oxidative stress, we determined urinary concentrations of a tetranordicarboxylic acid metabolite of F2‐isoprostanes (F2IP‐M) by mass spectrometry in 8 patients with scleroderma (representing a wide spectrum of disease, including limited disease with refractory digital ulceration or pulmonary hypertension, and diffuse disease) and in 10 healthy control subjects.Results. F2IP‐M concentrations were significantly higher in patients with scleroderma (mean ± SEM 3.41 ± 0.64 ng/mg of creatinine) than in healthy controls (1.22 ± 0.14 ng/mg of creatinine) (P = 0.002). These elevations occurred in patients with limited disease and in those with diffuse disease.Conclusion. The increased level of urinary F2IP‐M supports the hypothesis that free radical–induced oxidative injury occurs in scleroderma and provides a biologic marker whose relationship to disease activity and disease therapy may be important. These findings may also provide a rationale for exploring whether antioxidant therapy may influence the natural course of the disease.

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Section: Discussionmentioning

confidence: 98%

Evidence of free radical–mediated injury (isoprostane overproduction) in scleroderma

Stein

Tanner

Awad

et al. 1996

Arthritis & Rheumatism

154

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“…These 2 elements can thus overlap, jeopardizing the integrity of the vessel wall. In genetically predisposed SSc patients, characterized by ischemia and oxidative stress, 68 with raised levels of LDL undergoing oxidation, triggering vessel wall inflammation, 69 the overlap with SSc-dependent endothelial injury creates a noxious loop involving the microcirculation and macrocirculation. In this scenario, pathogenetic factors participating in endothelial sufferance, such as anti-endothelial cell antibodies, dysfunction of the fibrinolytic and coagulation system, and an increase of circulating levels of homocysteine, soluble intercellular adhesion molecule-1, and CRP may contribute significantly to increased risk of developing accelerated macrovascular disease.…”

Section: Macrovascular Disease and Atherosclerosis In Systemic Sclerosismentioning

confidence: 99%

Accelerated Atherosclerosis in Autoimmune Rheumatic Diseases

et al. 2005

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“…Reference Evidence in vivo Herrick et al [49] Reduced micronutrient antioxidants in SSc Levels of vitamin C, vitamin E, and other dietary antioxidants lower in SSc patients -suggests increased susceptibility to reactive oxygen species Bruckdorfer et al [50] Reduced in vitro LDL oxidation lag-time in SSc Oxidation lag time in vitro is reduced for LDL isolated from SSc patients' serum. Suggests greater susceptibility to oxidation in vivo.…”

Section: Potential Involvement Of Oxidant Stress In Systemic Sclerodementioning

confidence: 98%

Novel therapeutic strategies in scleroderma

Denton

Black

1999

Curr Rheumatol Rep

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Optimal management for scleroderma (systemic sclerosis) is likely to require treatment of the underlying disease process, which remains incompletely understood, and also of the organ-based complications of this heterogeneous condition. Clinical trials evaluating several potential agents have been completed recently, including D-penicillamine and interferon alpha. Unfortunately none of these studies has suggested significant efficacy. This article focuses on new treatment approaches using existing therapeutic agents, such as prostacyclin, and considers the potential usefulness of new agents (eg, relaxin, halofuginone) or strategies such as intensive immunosuppression with peripheral stem cell rescue. Ultimately, a better understanding of disease pathogenesis may facilitate the development of targeted therapy against key events or mediators, but for the present better evaluation of existing agents and a focus on optimizing protocols for organ-based complications, such as pulmonary vascular disease or hypertensive renal crisis, are important goals.

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Increased susceptibility to oxidation of low‐density lipoproteins isolated from patients with systemic sclerosis

Cited by 82 publications

References 37 publications

Evidence of free radical–mediated injury (isoprostane overproduction) in scleroderma

Evidence of free radical–mediated injury (isoprostane overproduction) in scleroderma

Accelerated Atherosclerosis in Autoimmune Rheumatic Diseases

Novel therapeutic strategies in scleroderma

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