[Hypoxia and angiogenesis in rheumatic diseases].
The important role of angiogenesis for the pathogenesis of most tumors has gained much interest into the mechanisms of new vessel formation during recent years. Hypoxia induces angiogenesis via stabilization of the transcription factor HIF-1alpha. After dimerization of HIF-1alpha with HIF-1beta/ARNT, HIF-1 binds to the hypoxia-responsive elements in the regulatory regions of proangiogenic molecules such as VEGF. Hypoxia-mediated angiogenesis also plays a part in the pathogenesis of rheumatoid arthritis. For instance, intraarticular application of the angiostatic molecule angiostatin reduces the severity of collagen-induced arthritis in mice. Moreover, recent data indicate that the expression of HIF-1alpha in myeloid cells is important for the initiation of the inflammatory infiltrate in rheumatoid arthritis. In contrast to rheumatoid arthritis, the therapeutic goal in systemic sclerosis (SSc) is the formation of new vessels rather than the inhibition of angiogenesis. Surprisingly, several proangiogenic factors such as VEGF or MCP-1 (CCL-2) are overexpressed in the skin of patients with SSc despite the reduction in the capillary density. The role of these findings for the defective angiogenesis in SSc is currently investigated in our laboratory.
Distler
K
K
Zentrum für Experimentelle Rheumatologie, Universitätsspital Zürich, Gloriastr. 25, 8091 Zürich, Switzerland. Oliver.Distler@usz.ch
D043165:Angiostatic Proteins / Q000502:physiology; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000503:physiopathology*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007596:Joints / Q000098:blood supply; D051379:Mice; D008833:Microcirculation / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D012595:Scleroderma, Systemic / Q000503:physiopathology*; D012867:Skin / Q000098:blood supply; D014157:Transcription Factors / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D043165:Angiostatic Proteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A