Morphologic Changes in the Digital Arteries of Patients with Progressive Systemic Sclerosis (Scleroderma) and Raynaud Phenomenon

150

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Anticentromere antibody as a predictor of digital ischemic loss in patients with systemic sclerosis

Wigley¹,

Wise²,

Rm³

et al. 1992

150

“…Potential mechanisms by which free radicals could be implicated in the pathogenesis of scleroderma include not only their ability to stimulate fibroblast proliferation and fibrosis (2), but also their effects on vascular responses. In addition to structural changes, altered vascular responses resulting in enhanced vasoconstriction are important in scleroderma (20). Free radicals may play a role in such altered vascular responses.…”

Section: Discussionmentioning

confidence: 99%

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

Stein

Tanner

Awad

et al. 1996

154

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.

“…Raynaud's phenomenon, increased thickness of the vascular wall, devascularization, and thickness of the basement membrane are typical features of SSc. The digital arteries of patients with SSc exhibit marked intimal proliferation, resulting in severe narrowing and occlusion of arterial lumen and limited vasodilative responses to vasodilator therapies (1).…”

mentioning

confidence: 99%

Comprehensive investigation of disease‐specific short peptides in sera from patients with systemic sclerosis: Complement C3f‐des‐arginine, detected predominantly in systemic sclerosis sera, enhances proliferation of vascular endothelial cells

Xiang¹,

Matsui²,

Matsuo³

et al. 2007

Objective. To identify pathogenic and/or diseasespecific short peptides in sera from patients with systemic sclerosis (SSc).Methods. Serum samples from 40 patients with SSc, 30 patients with systemic lupus erythematosus, 21 patients with rheumatoid arthritis, 30 patients with osteoarthritis, and 26 healthy donors were tested. Short peptides with molecular weights of smaller than ϳ3 kd, purified from the sera by magnetic bead-based hydrophobic interaction chromatography 18, were detected and their amino acid sequences determined using matrix-assisted laser desorption ionization-time-offlight mass spectrometry. Effects of the identified peptides on fibroblasts and microvascular endothelial cells were tested using synthesized peptides and sera containing the peptides.