Expression pattern of VEGFR-1,-2,-3 and D2-40 protein in the skin of patients with systemic sclerosis
Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan. European journal of dermatology: EJD
(Impact Factor: 1.99).
08/2011; 21(4):490-4. DOI: 10.1684/ejd.2011.1284
The earliest clinical symptoms of systemic sclerosis (SSc) relate to disturbances in the peripheral vascular system. However, detailed examination of the microcirculation including the lymphatics in the skin of patients with SSc has not been reported. The aim of our study was to examine the expression patterns of vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3 and the lymphatic endothelial cell marker D2-40 in the skin of SSc patients. Skin biopsy specimens from nine patients with SSc were analysed by immunohistochemistry using antibodies against VEGFR-1, VEGFR-2, VEGFR-3 and D2-40 protein. The lumen area of lymphatic vessels was measured. The data were statistically analysed using the Mann-Whitney U test, Wilcoxon signed-ranks or Spearman's rank correlation coefficient method. The intensity of VEGFR-2 and VEGFR-3 staining in the skin of patients with SSc was significantly higher than that in healthy controls. The lumen area of lymphatic vessels in the skin of patients with SSc was significantly larger than that in healthy controls. This study details the expression of VEGFR and D2-40 in the skin of patients with SSc, and highlights a possible role of microcirculatory dysfunction in the pathogenesis of systemic sclerosis.
- "Interestingly, serum VEGFR-1 level was reported to be high in patients with Crohn's disease . Increased serum VEGFR-1 in patients  seems contradictory to lack of increase in tissue level VEGFR-1 in animal studies of autoimmune diseases  , but for wound healing, we tend to believe that serum level VEGFR-1 is more likely to be increased in patients with IBD and SS which is also supported with the decreased sVEGFR levels. As a result of the decreased sVEGFR-1 level in IBD and SS, these patients will likely have excessive functions of VEGFR-1 which is characterized by relentless inflammation in these patients. "
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ABSTRACT: The pathophysiology of the chronicity and non-healing status of wounds remains unknown. This paper presents the following hypothesis: abnormal patterns of vascular endothelial growth factor receptors (VEGFRs) are the culprits of wound chronicity and non-healing. More specifically, for patients with poor circulation, the decreased VEGFR-2 level is the cause of poor wound healing; for patients with non-compromised circulation, for example, patients with concurrent chronic wounds and active autoimmune diseases, the increased VEGFR-1 level is related to the non-healing status of wounds. The hypothesis is supported by the following facts. VEGFR-1 is the main contributor for inflammation and VEGFR-2 facilitates angiogenesis; soluble VEGFR-1 (sVEGFR-1) inactivates both VEGFR-1 and VEGFR-2. Patients with auto-immune disease have abnormally increased VEGFR-1 and decreased sVEGFR. Wounds in patients with active autoimmune diseases have poor response to electric stimulation which facilitates chronic wound healing in patients without active autoimmune diseases via increasing vascular endothelial growth factor (VEGF) secretion. Patients with chronic wounds (including diabetic foot ulcers and venous leg ulcers) but no active autoimmune diseases have decreased VEGFR-2 levels. We thus believe that abnormal patterns of VEGFRs are the culprits of wound chronicity and non-healing. For wounds with compromised circulation, VEGFR-2 decrease contributes to its chronicity; whereas for wounds with non-compromised circulation, VEGFR-1 increase is the leading cause of the non-healing status of chronic wounds. Treatments and research in wound care should be tailored to target these changes based on circulation status of wounds. Complete elucidation of changes of VEGFRs in chronic and non-healing wounds will enhance our understandings in tissue healing and thus better our selection of appropriate treatments for chronic and non-healing wounds.
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