Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Seminars in Immunopathology
Published in: Seminars in Immunopathology 3/2008

01-07-2008 | Review

Oxidative stress and the pathogenesis of scleroderma: the Murrell’s hypothesis revisited

Authors: Armando Gabrielli, Silvia Svegliati, Gianluca Moroncini, Giovanni Pomponio, Mariarosaria Santillo, Enrico V. Avvedimento

Published in: Seminars in Immunopathology | Issue 3/2008

Login to get access

Abstract

Systemic sclerosis (SSc, scleroderma) is a devastating, immune-mediated, multisystem disorder characterized by microvasculature damage, circulating autoantibodies, and fibroblast activation, leading to massive fibrosis of skin, vessels, muscles, and visceral organs. Scleroderma causes disability and death as the result of end-stage organ failure. At present, no specific diagnostic nor therapeutic tools are available to handle the disease. In spite of significant effort, the etiology and pathogenesis of SSc remain obscure and, consequently, the disease outcome is unpredictable. Several years ago, Murrell suggested a unifying hypothesis linking the pathogenesis of scleroderma to the generation of a large excess of reactive oxygen species. This hypothesis has been substantiated by several reports indicating the presence of an abnormal redox state in patients with scleroderma. This review will summarize the available evidence supporting the link between free radicals and the main pathological features of scleroderma.
Literature
1.
Jimenez AS, Derk TC (2004) Following the molecular pathway toward an understanding of the pathogenesis of systemic sclerosis. Ann Intern Med 140:37–50PubMed
2.
Varga J, Abraham D (2007) Systemic sclerosis: a prototypic multisystem fibrotic disorder. J Clin Invest 117:557–567PubMed
3.
Murrell DF (1993) A radical proposal for the pathogenesis of scleroderma. J Am Acad Dermatol 28:78–85PubMed
4.
Herrick AL, Rieley F, Schofield D et al (1994) Micronutrient antioxidant status in patients with primary Raynaud’s phenomenon and systemic sclerosis. J Rheumatol 21:1477–1483PubMed
5.
Lundberg AC, Akesson A, Akesson B (1992) Dietary intake and nutritional status in patients with systemic sclerosis. Ann Rheum Dis 51:1143–1148PubMedCrossRef
6.
Bruckdorfer KR, Hillary JB, Bunce T et al (1995) Increased susceptibility to oxidation of low-density lipoproteins isolated from patients with systemic sclerosis. Arthritis Rheum 38:1060–1067PubMed
7.
Iwata Y, Ogawa F, Komura K et al (2007) Autoantibody against peroxiredoxin I, an antioxidant enzyme, in patients with systemic sclerosis: possible association with oxidative stress. Rheumatology 46:790–795PubMed
8.
Tikly M, Channa K, Theodorou P et al (2006) Lipid peroxidation and trace elements in systemic sclerosis. Clin Rheumatol 25:320–324PubMed
9.
Stein CM, Tanner SB, Awad JA et al (1996) Evidence of free radical-mediated injury (isoprostane overproduction) in scleroderma. Arthritis Rheum 39:1146–1150PubMed
10.
Cracowski JL, Marpeau C, Carpentier PH et al (2001) Enhanced in vivo lipid peroxidation in scleroderma spectrum disorders. Arthritis Rheum 44:1143–1148PubMed
11.
Cracowski JL, Carpentier PH, Imbert B et al (2002) Increased urinary F2-isoprostanes in systemic sclerosis, but not in primary Raynaud’s phenomenon: effect of cold exposure. Arthritis Rheum 4:1319–1323
12.
Volpe A, Biasi D, Caramaschi P et al (2006) Levels of F2-isoprostanes in systemic sclerosis: correlation with clinical features. Rheumatology 45:314–320PubMed
13.
Balbir-Gurman A, Braun-Moscovici Y, Livshitz V et al (2007) Antioxidant status after iloprost treatment in patients with Raynaud’s phenomenon secondary to systemic sclerosis. Clin Rheumatol 26:1517–1521PubMed
14.
Beckman JS, Beckman TW, Chen J et al (1990) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Aca Sci U S A 87:1620–24
15.
Clancy RM, Amin AR, Abramson SB (1998) The role of nitric oxide in inflammation and immunity. Arthritis Rheum 41:1141–1151PubMed
16.
Matucci CM, Kahaleh MB (2002) Beauty and the beast. The nitric oxide paradox in systemic sclerosis. Rheumatology 41:843–847
17.
Yamamoto Y, Katayama I, Nishioka K (1998) Nitric oxide production and inducible nitric oxide synthase expression in systemic sclerosis. J Rheumatol 25:314–317PubMed
18.
Dooley A, Gao B, Bradley N et al (2006) Abnormal nitric oxide metabolism in systemic sclerosis: increased levels of nitrated proteins and asymmetric dimethylarginine. Rheumatology 45:676–684PubMed
19.
Takagi K, Kawaguchi Y, Hara M et al (2003) Serum nitric oxide (NO) levels in systemic sclerosis patients: correlation between NO levels and clinical features. Clin Exp Immunol 134:538–544PubMed
20.
Allanore Y, Borderie D, Hilliquin P et al (2001) Low levels of nitric oxide (NO) in systemic sclerosis: inducible NO synthase production is decreased in cultured peripheral blood monocyte/macrophage cells. Rheumatology 40:1089–1096PubMed
21.
Cotton A, Herrick AL, Jayson MI et al (1999) Endothelial expression of nitric oxide synthases and nitrotyrosine in systemic sclerosis. J Pathol 189:273–278PubMed
22.
Kharitonov SA, Cailes JB, Black CM et al (1997) Decreased nitric oxide in the exhaled air of patients with systemic sclerosis with pulmonary hypertension. Thorax 52:1051–1055PubMedCrossRef
23.
Moodley YP, Lalloo UG (2001) Exhaled nitric oxide is elevated in patients with progressive systemic sclerosis without interstitial lung disease. Chest 119:1449–1454PubMed
24.
Malerba M, Radaeli A, Ragnoli B et al (2007) Exhaled nitric oxide levels in systemic sclerosis with and without pulmonary involvement. Chest 132:575–580PubMed
25.
Tiev KP, Cabane J, Aubourg F et al (2007) Severity of scleroderma lung disease is related to alveolar concentration of nitric oxide. Eur Respir J 30:26–30PubMed
26.
Rolla G, Colagrande P, Scappaticci E et al (2000) Exhaled nitric oxide in systemic sclerosis: relationships with lung involvement and pulmonary hypertension. J Rheumatol 27:1693–1698PubMed
27.
Sambo P, Amico D, Giacomelli R et al (2001) Intravenous N-acetylcysteine for treatment of Raynaud’s phenomenon secondary to systemic sclerosis: a pilot study. J Rheumatol 28:2257–2262PubMed
28.
Herrick AL, Hollis S, Schofield D et al (2000) A double-blind placebo-controlled trial of antioxidant therapy in limited cutaneous systemic sclerosis. Clin Exp Rheumatol 18:349–356PubMed
29.
Denton CP, Bunce TD, Dorado MB et al (1999) Probucol improves symptoms and reduces lipoprotein oxidation susceptibility in patients with Raynaud’s phenomenon. Rheumatology 38:309–315PubMed
30.
Becker LB (2004) New concepts in reactive oxygen species and cardiovascular reperfusion physiology. Cardiovasc Res 61:461–470PubMed
31.
Sambo P, Jannino L, Candela M et al (1999) Monocytes of patients with systemic sclerosis (scleroderma) spontaneously release in vitro increased amounts of superoxide anion. J Invest Dermatol 112:78–84PubMed
32.
Cracowski JL, Kom GD, Salvat-Melis M et al (2006) Postocclusive reactive hyperemia inversely correlates with urinary 15-F2t-isoprostane levels in systemic sclerosis. Free Radic Biol Med 40:1732–1737PubMed
33.
Sambo P, Svegliati Baroni S, Luchetti M et al (2001) Oxidative stress in scleroderma. Maintenance of scleroderma fibroblast phenotype by the constitutive up-regulation of reactive oxygen species generation through the NADPH oxidase complex pathway. Arthritis Rheum 44:2653–2664PubMed
34.
Svegliati Baroni S, Cancello R, Sambo P et al (2005) PDGF and reactive oxygen species (ROS) regulate Ras protein levels in primary human fibroblasts via ERK 1/2. Amplification of ROS-ERK-Ras signalling in systemic sclerosis fibroblasts. J Biol Chem 280:36474–36482
35.
Allanore Y, Borderie D, Périanin A et al (2005) Nifedipine protects against overproduction of superoxide anion by monocytes from patients with systemic sclerosis. Arthritis Res Ther 7:R93–R100PubMed
36.
Failli P, Palmieri L, D’Alfonso C et al (2002) Effect of N-acetyl-l-cysteine on peroxynitrite and superoxide anion production pf lung alveolar macrophage in systemic sclerosis. Nitric Oxide 7:277–282PubMed
37.
Yamamoto T, Sawada Y, Katayama I et al (1998) Increased production of nitric oxide stimulated by interleukin-1beta in peripheral blood mononuclear cells in patients with systemic sclerosis. Br J Rheumatol 37:1123–1125PubMed
38.
Bedard K, Krause KE (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87:245–313PubMed
39.
Lassegue B, Sorescu D, Szocs K et al (2001) Novel gp91 (phox) homologues in vascular smooth muscle cells: nox1 mediates angiotensin II-induced superoxide formation and redox-sensitive signalling pathway. Circ Res 88:888–894PubMed
40.
Touyz RM, Chen X, Tabet F et al (2002) Expression of a functionally active gp91phox-containing neutrophil-type NAD(P)H oxidase in smooth muscle cells from human resistance arteries: regulation by angiotensin II. Circ Res 90:1205–1213PubMed
41.
Cucoranu I, Clempus R, Dikalova A et al (2005) NAD(P)H oxidase 4 mediates transforming growth factor-beta-1-induced differentiation of cardiac fibroblasts into myofibroblasts. Circ Res 97:900–907PubMed
42.
Sturrock A, Cahill B, Norman K et al (2005) Transforming growth factor beta1 induces Nox4 NAD(P)H oxidase and reactive oxygen species-dependent proliferation in human pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 290:L661–L673PubMed
43.
Neufeld G, Cohen T, Gengrinovitch S et al (1999) Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 13:9–22PubMed
44.
Thannickal VJ, Fanburg BL (1995) Activation of an H2O2-generating NADH in human lung fibroblasts by transforming growth factor-beta 1. J Biol Chem 270:30334–30338PubMed
45.
Chapple ILC (1997) Reactive oxygen species and antioxidants in inflammatory diseases. J Clin Periodontol 24:287–296PubMed
46.
Datla RS, Peshavariya H, Dusting GJ et al (2007) Important role of Nox4 type NADPH oxidase in angiogenic responses in human microvascular endothelial cells in vitro. Arterioscler Thromb Vasc Biol 27:2319–2324PubMed
47.
Ago T, Kitazono T, Ooboshi H et al (2004) Nox4 as the major catalytic component of an endothelial NAD(P)H oxidase. Circulation 109:227–233PubMed
48.
Ago T, Kitazono T, Kuroda J et al (2005) NAD(P)H oxidase in rat basilar arterial endothelial cells. Stroke 36:1040–1046PubMed
49.
Banfi B, Malgrange B, Knisz J et al (2004) Nox3: a superoxide-generating NADPH oxidase of the inner ear. J Biol Chem 279:46065–46072PubMed
50.
Furst R, Brueckl C, Kuebler WM et al (2005) Atrial natriuretic peptide induces mitogen-activated protein kinase phosphatase-1 in human endothelial cells via Rac1 and NAD(P)H oxidase/Nox2-activation. Circ Res 96:43–53PubMed
51.
Goyal P, Weissmann N, Grimminger F et al (2004) Upregulation of NAD(P)H oxidase 1 in hypoxia activates hypoxia-inducible factor 1 via increase in reactive oxygen species. Free Radic Biol Med 36:1279–1288PubMed
52.
Higgings DF, Kimura K, Bernhardt WM et al (2007) Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition. J Clin Invest 117:3810–3820
53.
Colston JT, de la Rosa SD, Strader JR et al (2005) H2O2 activates Nox4 through PLA2-dependent arachidonic acid production in adult cardiac fibroblasts. FEBS Lett 579:2533–2540PubMed
54.
Dhaunsi GS, Paintlia MK, Kaur J et al (2004) NADPH oxidase in human lung fibroblasts. J Biomed Sci 11:617–622PubMed
55.
Chamseddine AH, Miller JFJ (2003) gp91phox contributes to NADPH oxidase activity in aortic fibroblasts, but not smooth muscle cells. Am J Physiol Heart Circ Physiol 285:H2284–H2289PubMed
56.
Harris ML, Rosen A (2003) Autoimmunity in scleroderma: the origin, pathogenetic role and clinical significance of autoantibodies. Curr Opin Rheumatol 15:778–784PubMed
57.
Hasegawa M, Sato S, Fujimoto M et al (1998) Serum levels of interleukin 6 (IL-6) oncostatin M, soluble IL-6 receptor, and soluble gp130 in patients with systemic sclerosis. J Rheumatol 25:308–313PubMed
58.
Hasegawa M, Fujimoto M, Kikuchi K et al (1997) Elevated serum levels of interleukin 4 (IL-4), IL-10 and IL-13 in patients with systemic sclerosis. J Rheumatol 24:328–332PubMed
59.
Valentini G, Baroni A, Esposito K et al (2001) Peripheral blood T lymphocytes from systemic sclerosis patients show both Th1 and Th2 activation. J Clin Immunol 21:210–217PubMed
60.
Hesegawa M, Sato S, Ihn H et al (1999) Enhanced production of interleukin-6 (IL-6) oncostatin M and soluble IL-6 receptor by cultured peripheral blood mononuclear cells from patients with systemic sclerosis. Rheumatology 38:612–617
61.
Mavalia C, Scaletti C, Romagnani P et al (1997) Type 2 helper T-cell predominance and high CD30 expression in systemic sclerosis. Am J Pathol 151:1751–1758PubMed
62.
Li-Weber M, Giaisi M, Treiber MK et al (2002) Vitamin E inhibits IL-4 gene expression in peripheral blood T cells. Eur J Immunol 32:2401–2408PubMed
63.
King MR, Ismail AS, Davis LS et al (2006) Oxidative stress promotes polarization of human T cell differentiation toward a T helper 2 phenotype. J Immunol 176:2765–2772PubMed
64.
Ishikawa H, Carrasco D, Claudio E et al (1997) Gastric hyperplasia and increased proliferative responses of lymphocytes in mice lacking the COOH-terminal ankyrin domain of NF-kappaB2. J Exp Med 186:999–1014PubMed
65.
Casciola-Rosen L, Wigley F, Rosen A (1997) Scleroderma autoantigens are uniquely fragmented by metal-catalyzed oxidation reactions: implication for pathogenesis. J Exp Med 185:71–79PubMed
66.
Obata F, Hoshino A, Toyama A (2006) Hydrogen peroxide increases interleukin-12 p40/p70 molecular ratio and induces Th2 predominant responses in mice. Scand J Immunol 63:125–130PubMed
67.
Peterson JD, Herzenberg LA, Vasquez K et al (1998) Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns. Proc Natl Acad Sci U S A 95:3071–3076PubMed
68.
Jeannin P, Delneste Y, Lecoanet-Henchoz S et al (1995) Thiols decrease human interleukin (IL) 4 production and IL-4-induced immunoglobulin synthesis. J Exp Med 182:1785–1792PubMed
69.
Prescott RJ, Freemont AJ, Jones CJ et al (1992) Sequential dermal microvascular and perivascular changes in the development of scleroderma. J Pathol 166:255–263PubMed
70.
Fleischmajer R, Perlish JS, Shaw KV et al (1976) Skin capillary changes in early systemic scleroderma. Electron microscopy and “in vitro” autoradiography with tritiated thymidine. Arch Dermatol 112:1553–1557PubMed
71.
Fleischmajer R, Perlish JS (1980) Capillary alterations in scleroderma. J Am Acad Dermatol 2:161–170PubMed
72.
Mitchell RN, Libby P (2007) Vascular remodelling in transplant vasculopathy. Circ Res 100:967–978PubMed
73.
Kuwana M, Okazaki Y, Yasuoka H et al (2004) Defective vasculogenesis in systemic sclerosis. Lancet 364:603–610PubMed
74.
Sgonc R, Gruschwitz MS, Dietrich H et al (1996) Endothelial cell apoptosis is a primary pathogenetic event underlying skin lesions in avian and human scleroderma. J Clin Invest 98:785–792PubMed
75.
Herron GS, Luz I, Romero LI (1998) Vascular abnormalities in scleroderma. Semin Cutan Med Surg 17:12–17PubMed
76.
Griendling KK, Sorescu D, Ushio-Fukai M (2000) NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 86:494–501PubMed
77.
Lassègue B, Sorescu D, Szöcs K et al (2001) Novel gp91 (phox) homologues in vascular smooth muscle cells: nox1 mediates angiotensin II-induced superoxide formation and redox-sensitive signaling pathways. Circ Res 88:888–894PubMed
78.
Marumo T, Schini-Kerth VB, Fissilthaler B et al (1997) Platelet-derived growth factor-stimulated superoxide anion production modulates activation of transcription factor NF-kappaB and expression of monocyte chemoattractant protein 1 in human aortic smooth muscle cells. Circulation 96:2361–2367PubMed
79.
Wang Z, Castresana MR, Newman WH (2004) Reactive oxygen species-sensitive p38 MAPK controls thrombin-induced migration of vascular smooth muscle cells. J Mol Cell Cardiol 36:49–56PubMed
80.
Zhang H, Schmeisser A, Garlichs CD et al (1999) Angiotensin II-induced superoxide anion generation in human vascular endothelial cells: role of membrane-bound NADH-/NADPH-oxidases. Cardiovasc Res 44:215–222PubMed
81.
Pedruzzi E, Guichard C, Ollivier V (2004) NAD(P)H oxidase Nox-4 mediates 7-ketocholesterol-induced endoplasmic reticulum stress and apoptosis in human aortic smooth muscle cells. Mol Cell Biol 24:10703–10717PubMed
82.
Ushio-Fukai M, Zafari AM, Fukui T, Ishizaka N, Griendling KK (1996) p22phox is a critical component of the superoxide-generating NADH/NADPH oxidase system and regulates angiotensin II-induced hypertrophy in vascular smooth muscle cells. J Biol Chem 271:23317–23321PubMed
83.
Rey FE, Pagano PJ (2002) The reactive adventitia: fibroblasts oxidase in vascular function. Thromb Vasc Biol 22:1962–1971
84.
Kawaguchi Y, Takagi K, Hara M et al (2004) Angiotensin II in the lesional skin of systemic sclerosis patients contributes to tissue fibrosis via angiotensin II type 1 receptors. Arthritis Rheum 50:216–226PubMed
85.
Holland JA, Meyer JW, Chang MM et al (1998) Thrombin stimulated reactive oxygen species production in cultured endothelial cells. Endothelium 6:113–121PubMed
86.
Bogatkevich GS, Gustio E, Oates JC et al (2004) Distinct PKC isoforms mediate cell survival and DNA synthesis in thrombin-induced myofibroblasts. Am J Physiol Lung Cell Mol Physiol 288:L190–L201PubMed
87.
Klareskog L, Gustaffson R, Scheynius A et al (1990) Increased expression of platelet-derived growth factor type B receptors in the skin of patients with systemic sclerosis. Arthritis Rheum 33:1534–1541PubMed
88.
Xue-yi Z, Jan-zhong Z, Ping T et al (1998) Expression of platelet-derived growth factor B chain and platelet-derived growth factor b-receptor in fibroblasts of scleroderma. J Dermatol Sci 18:90–97
89.
Abraham DJ, Varga J (2005) Scleroderma: from cell and molecular mechanisms to disease models. Trends Immunol 26:587–595PubMed
90.
Murrell GAC, Francis MJO, Bromley L (1990) Modulation of fibroblast proliferation by oxygen free radicals. Biochem J 265:659–665PubMed
91.
Falanga V, Martin TA, Takagi H et al (1993) Low oxygen tension increases mRNA levels of alpha 1(I) procollagen in human dermal fibroblasts. J Cell Physiol 157:408–412PubMed
92.
Parola M, Pinzani M, Casini A et al (1993) Stimulation of lipid peroxidation or 4-hydroxynonenal treatment increases procollagen a(I) gene expression in human liver fat-storing cells. Biochem Biophys Res Commun 194:1044–1050PubMed
93.
Kinnula VL, Fattman CL, Tan RJ et al (2005) Oxidative stress in pulmonary fibrosis. A possible role for redox modulatory therapy. Am J Respir Crit Care Med 172:417–422PubMed
94.
Shi Y, Massagué J (2003) Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 113:685–700PubMed
95.
Trojanowska M (2002) Molecular aspects of scleroderma. Front Biosci 7:608–618
96.
Bellocq A, Azoulay E, Marullo S et al (1999) Reactive oxygen species and nitrogen intermediates increase transforming growth factor-beta 1 release from human epithelial alveolar cells through two different mechanisms. Am J Respir Cell Mol Biol 21:128–136PubMed
97.
Barcellos-Hoff MH, Dix TA (1996) Redox-mediated activation of latent transforming growth factor beta. Mol Endocrinol 10:1077–1083PubMed
98.
Hancock JT, Desikan R, Neill SJ (2001) Role of reactive oxygen species in cell signalling pathways. Biochem Soc Trans 29:345–350PubMed
99.
Sementchenko VI, Watson DK (2000) Ets target genes: past, present and future. Oncogene 19(55):6533–6548PubMed
100.
Arsalane K, Dubois CM, Muanza T et al (1997) Transforming growth factor-beta 1 is a potent inhibitor of glutathione synthesis in the lung epithelial cell line A 549: transcription effect on the GSH rate-limiting enzyme gamma-glutamylcysteine synthetase. Am J Respir Cell Mol Biol 17:599–607PubMed
101.
Factor VM, Kiss A, Woitach JT et al (1998) Disruption of redox homeostasis in the transforming growth factor-alpha/c-myc transgenic mouse model of accelerated hepatocarcinogenesis. J Biol Chem 273:15846–15853PubMed
102.
Ask K, Martin GE, Kolb M et al (2006) Targeting genes for treatment in idiopathic pulmonary fibrosis: challenges and opportunities, promises and pitfalls. Proc Am Thorac Soc 3:389–393PubMed
103.
Hoyle GW, Li J, Finkelstein JB et al (1999) Emphysematous lesions, inflammation, and fibrosis in the lungs of transgenic mice overexpressing platelet-derived growth factor. Am J Pathol 154:1763–1775PubMed
104.
Bae SY, sung JY Kim OS et al (2000) Platelet-derived growth factor-induced H2O2 production requires the activation of phosphatidylinositol 3-kases. J Biol Chem 275:10527–10531PubMed
105.
Park J, Ha H, Ahn HJ et al (2005) Sirolimus inhibits platelet-derived growth factor-induced collagen synthesis. Transplant Proc 37:3459–3462PubMed
106.
Rajkumar VS, Howelll K, Csiszar K et al (2005) Shared expression of phenotypic markers in systemic sclerosis indicates convergence of pericytes and fibroblasts to a myofibroblast lineage in fibrosis. Arthritis Res Ther 7:R1113–R1123PubMed
107.
Distler JH, Jungel A, Huber LC et al (2007) Imatinib mesylate reduces production of extracellular matrix and prevents development of experimental dermal fibrosis. Arthritis Rheum 56:311–322PubMed
108.
Svegliati Baroni SS, Santillo MR, Bevilacqua F et al (2006) Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis (scleroderma). N Engl J Med 354:2667–2676
Metadata
Title
Oxidative stress and the pathogenesis of scleroderma: the Murrell’s hypothesis revisited
Authors
Armando Gabrielli
Silvia Svegliati
Gianluca Moroncini
Giovanni Pomponio
Mariarosaria Santillo
Enrico V. Avvedimento
Publication date
01-07-2008
Publisher
Springer-Verlag
Published in
Seminars in Immunopathology / Issue 3/2008
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI
https://doi.org/10.1007/s00281-008-0125-4

Other articles of this Issue 3/2008

Seminars in Immunopathology 3/2008 Go to the issue

Review

Hyperinflammation in chronic granulomatous disease and anti-inflammatory role of the phagocyte NADPH oxidase

Letter to the Editor

Remarks on the article Genetics and immunopathology of chronic granulomatous disease by Marie José Stasia and Xing Jun Li

Letter to the Editor

Reply to the remarks by Joachim Roesler on the article Genetics and immunopathology of chronic granulomatous disease

Review

NOX enzymes and diabetic complications

Review

The NADPH oxidase NOX2 plays a role in periodontal pathologies

Review

Nox enzymes and oxidative stress in the immunopathology of the gastrointestinal tract
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits