tailieunhanh - Báo cáo y học: "Hypoxia in the pathogenesis of systemic sclerosis"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: Hypoxia in the pathogenesis of systemic sclerosis. | Available online http content 11 2 220 Review Hypoxia Hypoxia in the pathogenesis of systemic sclerosis Christian Beyer1 Georg Schett1 Steffen Gay2 Oliver Distler2 and Jorg HW Distler1 1 Department of Internal Medicine 3 and Institute for Clinical Immunology University of Erlangen-Nuremberg 91054 Erlangen Germany 2Center of Experimental Rheumatology and Center of Integrative Human Physiology Department of Rheumatology University Hospital Zurich CH-8091 Zurich Switzerland Corresponding author Oliver Distler Published 21 April 2009 This article is online at http content 11 2 220 2009 BioMed Central Ltd Arthritis Research Therapy 2009 11 220 doi ar2598 Abstract Autoimmunity microangiopathy and tissue fibrosis are hallmarks of systemic sclerosis SSc . Vascular alterations and reduced capillary density decrease blood flow and impair tissue oxygenation in SSc. Oxygen supply is further reduced by accumulation of extracellular matrix ECM which increases diffusion distances from blood vessels to cells. Therefore severe hypoxia is a characteristic feature of SSc and might contribute directly to the progression of the disease. Hypoxia stimulates the production of ECM proteins by SSc fibroblasts in a transforming growth factor-p-dependent manner. The induction of ECM proteins by hypoxia is mediated via hypoxia-inducible factor-1 a-dependent and -independent pathways. Hypoxia may also aggravate vascular disease in SSc by perturbing vascular endothelial growth factor VEGF receptor signalling. Hypoxia is a potent inducer of VEGF and may cause chronic VEGF over-expression in SSc. Uncontrolled over-expression of VEGF has been shown to have deleterious effects on angiogenesis because it leads to the formation of chaotic vessels with decreased blood flow. Altogether hypoxia might play a central role in pathogenesis of SSc by augmenting vascular disease and tissue fibrosis. Introduction Oxygen homeostasis is a