The Expression Of HIF-1α,VEGF And Its Correlation With MVD In Psoriasis

Objective: Psoriasis (PS) is a chronic replapsing inflammatory dermatosis. Epidermal hyperplasia and angiogenesis in papillary dermis constitute the major pathology characteristics of psoriasis. Pathogenetic factors involve genetic factor and environmental stimuli. Although the first stimulus of inflammation is unknown origin, angiogenesis is indispensable for infiltration of neutrophils and lymphocytes. And angiogenesis is obviously related to pathogenesis, lasting and relapse of PS. In most angiogenic factors, vascular endothelial growth factor (VEGF) is main stimulating factor, which can cause vascular endothelial cell proliferate, enhance the permeability of the microvesles and promote the migrating of the endothelial cell and mononuclear cell to the lesion. Some evidences suggested that VEGF upregulation is an early and important step in the pathophysiology of psoriasis. At present, various factors that influence VEGF have being the investigative focus of psoriasis. Hypoxia-inducible factors-1 (HIF-1) is a transcription active neucleoprotein that forms in the hypoxia condition and can adapt cells the hypoxia environmemt. In psoriasis, the cell proliferation could increase oxygen cost and the epidermal thickening could lead to impaired oxygen supply, and HIF-1αcan perfectly respond to anaerobic condition of organism. VEGF can contribute to angiogenesis of psoriasis, while VEGF can be activated by HIF-1α. Now it is the beginning that HIF-1αhas been studied in dermatosis.In order to research HIF-1αexpression and the relations beween HIF-1αand the angiogenesis in psoriasis, we detected HIF-1αand VEGF proteins in psoriasis with the method of immunohistochemistry, and used CD34 to mark vascular endothelial cells and counted microvessel density (MVD).Methods: 32 patients with psoriasis diagnosed by clinic and histopathology were collected from the dermatology department of the Forth Affiliated Hospital of Heibei University from October, 2004 to March, 2007. The expressions of HIF-1α, VEGF and CD34 in these patients were detected by immunohistochemical method. 30 healthy skin specimens from the surgery department were taken as controls. There were no significant differences in sex, age and locus of biopsy between controls and patients.Paraffin section was used by HE staining in histophathology and by histostain-SP methed in immunohistochemistry. The data was analyzed by SPSS 15.0 Mann-Whitney U rank test, t-test and Spearman rank correlation analysis.Results:1 The expression of HIF-1α: HIF-1αwas distributed mainly in the cytoplasm of epidermal keratinocytes and capillary endothelial cells and a small amount of perivascular inflammatory cells in the dermal papilla. And showed 25of 32 cases with psoriasis were positive, including 7 strong positive, 9 positive, 9 weakly positive and 7 negative. In the normal controls, it was found that 14 cases were negative, 5 weakly positive, 1 positive, and expressed mainly in the basal layer. In the dermis there were 1 strong positive, 6 positive, 15 weakly positive and 10 negative of 32 cases with PS, while all the cases of controls were negative. The results showed there were statistically significant differences beween PS and controls (P<0.01). Expression of HIF-1αin active stage was higher than in stable stage (P <0.05) and there was no significant difference among the gender, age and duration of the disease (P> 0.05).2 The expression of VEGF: VEGF was mainly located in the cytoplasm of keratinocytes, the vascular endothelial cells and inflammatory cells of dermal paplla. In epidermis, VEGF expression were found in 26 cases with PS , including 5 strongly positive, 9 positive, 12 weakly positive and 6 negative .and in the dermis 2 strong positive, 8 positive, 15 weakly positive, 7 negative. But in the controls, VEGF were only expressed positively or weak positively in the basal layer of epidermis and no in the vascular endothelial cells and inflammatory cells of dermis. The results indicated that VEGF expression in the patients with PS was higher than in the controls (P <0.01) and in the active stage higher than in the stable stage (P <0.05), showing significant difference. But there was no significant difference among gender, age and duration of the disease (P> 0.05).3 The expression of CD34: The CD34 was mainly stained in the vascular endothelial cells of dermis. Compared the value of the MVD between the two groups, it is indicated the MVD value was higher in the PS patients than in the controls and in active stage than stable stage, showing the significantly difference (P<0.05).4 There was a positive correlation between the expression of HIF-1αand VEGF in psoriasis (P<0.05). The coefficient correlation rs= 0.791.5 MVD is a quantitative indicator of angiogenesis. It was resulted that the mean value of MVD was higher in the patients with HIF-1αexpression than in the patients without HIF-1αexpression, showing statistically significant differences (P<0.05).Conclusions:1 The HIF-1αexpression in psoriatic skin is higher than controls. It is suggested that hypoxia and hypoxia reaction occured in psoriasis with increased oxygen consumption and impaired oxygen supply duing to cell proliferation and epidermal thickening. The HIF-1αexpression in the active stage was higher than in the stable stage, hinting that HIF-1αmight be related to the progression of the disease.2 The VEGF expression in patients is higher than in controls and in the active stage higher than in the stable stage of psoriasis, which hint that it take part in angiogenesis of psoriasis and might be related to the progression of it .3 MVD was significantly higher in the patients with PS than that in controls and in the active stage higher than in the stable stage of PS, suggesting that angiogenesis in psoriasis significantly higher than in controls and it can be used as an indicator of the condition of the disease.4 There was a positive correlation between HIF-1αand VEGF in psoriasis, suggesting that hypoxia may activate HIF-1αand HIF-1αactivates VEGF, which contribute to angiogenesis.5 The mean of MVD with HIF-1αexpression is higher than that without HIF-1αexpression, suggesting that HIF-1αrelated to angiogenesis.