Distler, Oliver and Distler, Joerg H. W. and Scheid, Annette and Acker, Till and Hirth, Astrid and Rethage, Janine and Michel, Beat A. and Gay, Renate E. and Mueller-Ladner, Ulf and Matucci-Cerinic, Marco and Plate, Karl H. and Gassmann, Max and Gay, Steffen (2004) Uncontrolled expression of vascular endothelial growth factor and its receptors leads to insufficient skin angiogenesis in patients with systemic sclerosis. CIRCULATION RESEARCH, 95 (1). pp. 109-116. ISSN 0009-7330,
Full text not available from this repository. (Request a copy)Abstract
Systemic sclerosis (SSc) skin lesions are characterized by disturbed vessel morphology with enlarged capillaries and an overall reduction in capillary density, suggesting a deregulated, insufficient angiogenic response. It has been postulated that this phenomenon is due to reduced expression of the potent angiogenic factor vascular endothelial growth factor (VEGF). In contrast to this hypothesis, we demonstrate that the expression of both VEGF and its receptors VEGFR-1 and VEGFR-2 is dramatically upregulated in skin specimens of SSc patients throughout different disease stages. Interestingly, upregulation of VEGF was not mediated by hypoxia-inducible transcription factor-1 (HIF-1) as indicated by only a weak expression of the oxygen-sensitive alpha-subunit of HIF-1 in the skin of SSc patients. This was unexpected on measuring low PO2 values in the SSc skin by using a polarographic oxygen microelectrode system. Considering our observation that PDGF and IL-1beta costimulated VEGF expression, we propose that chronic and uncontrolled VEGF upregulation that is mediated by an orchestrated expression of cytokines rather than VEGF downregulation is the cause of the disturbed vessel morphology in the skin of SSc patients. Consequently, for therapeutic approaches aiming to improve tissue perfusion in these patients, a controlled expression and timely termination of VEGF signaling appears to be crucial for success of proangiogenic therapies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PERIPHERAL-BLOOD MONOCYTES; ANGIOSTATIC FACTORS; UP-REGULATION; SCLERODERMA; HYPOXIA; VEGF; HIF-1-ALPHA; PLATELET; NEOVASCULARIZATION; FIBROBLASTS; angiogenesis; vascular endothelial growth factor; hypoxia-inducible transcription factor-1 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Jul 2021 06:50 |
| Last Modified: | 07 Jul 2021 06:50 |
| URI: | https://pred.uni-regensburg.de/id/eprint/37446 |
Actions (login required)
 |
View Item |
