Study On The Anti-angiogenesis Effect Of Psoralen Ultraviolet A Therapy And Vascular Endothelial Growth Factor Single Nucleotide Polymorphism In Chinese Patients With Psoriasis

Psoriasis is a common,chronic inflammatory skin disorder.The key histologic events in a plaque of psoriasis include abnormal keratinocyte proliferation and differentiation,inflammation,and vascular expansion.Microvascular changes within plaques of psoriasis include dilatation,tortuosity,increased permeability,and endothelial cell proliferation within the venous limb of capillaries in the dermal papillae. Skin lesional microvessel density (MVD) and mast cell density were detected by immunohistochemical method with monoclonal antibody specific for the endothelial marker CD34 and mast cell marker tryptase in patients with psoriasis and healthy subjects.αVβ3 integrin expression was detected by immunohistochemical method and level of vascular endothelial growth factor (VEGF) in sera was measured using enzyme-linked immunosorbent assay in patients with psoriasis and healthy subjects.We also study the effect of psoralen ultravioletA (PUVA) therapy on skin lesional MVD, mast cell density, αVβ3 integrin expression and serum (VEGF) level in patients with psoriasis. MVD in the skin lesions of psoriasis was higher than that in normal control(19.42±9.36vs4.18±1.84, P<0.01). Mast cell density in the skin lesions of psoriasis was higher than that in normal control(17.27±7.25vs8±1.89,P<0.01).The expression of αVβ3 integrin in lesional skin of psoriasis was higher than that in normal control. Serum levels of VEGF were significantly increased in psoriasis as compared with normal control. MVD and mast cell density in the skin lesions were significantly decreased in patients with psoriasis after PUVA therapy. The expression of α V β 3 integrin in lesional skin and serum VEGF levels were significantly decreased in patients with psoriasis after PUVA therapy. 3 It is indicated that the mechanism of PUVA therapy in psoriasis may involve anti-angiogenesis. Two VEGF single nucleotide polymorphism,a GC at -634 in the 5'-untranslated region and a CT at +936 in the 3'-untranslated region are useful for association studies as they occur at highest frequency in this area of the gene and have been implicated as candidate SNP in other diseases with a putative angiogenic basis.A significant correlation has been observed between VEGF protein production and the polymorphism-634, within the 5'-untranslated region of the VEGF gene in healthy subjects. VEGF plasma levels were significantly lower in carriers of VEGF +936T allele than those in noncarriers .We postulated that patients with psoriasis may have altered systemic expression of VEGF consequent upon programming at the genomic level.We examined the genotype frequency of the VEGF SNP -634 in psoriasis and in healthy individuals by TaqMan-MGB and fluorescence PCR method.For genotyping VEGF +936 polymorphism,the PCR restriction fragment length polymorphism (PCP-RFLP)method was performed. The frequency of VEGF -634 genotype and allele were not different from those in the control group.There was no difference in the frequency of VEGF +936 genotype and allele. VEGF-634?+936 single nucleotide polymorphism might not affect psoriasis susceptibility.