Luengas-Martinez Andrea, Ismail Dina, Paus Ralf, Young Helen S
Centre for Dermatology Research and Manchester Academic Health Science Centre The University of Manchester Manchester UK.
Dr. Philip Frost Department of Dermatology and Cutaneous Surgery University of Miami Miller School of Medicine Miami Florida USA.
Skin Health Dis. 2023 May 15;3(5):e245. doi: 10.1002/ski2.245. eCollection 2023 Oct.
Vascular Endothelial Growth Factor (VEGF)-A-mediated angiogenesis participates in the pathogenesis of psoriasis, thus inviting the hypothesis that anti-VEGF-A therapy could be beneficial in psoriasis. While anti-angiogenic agents are used in oncology and ophthalmology, these therapeutic strategies remain unexplored for the management of psoriasis.
Our objective was to investigate ex vivo how VEGF-A blockade impacts blood vessels, epidermis and immune cells in organ-cultured plaque and non-lesional skin from patients with psoriasis.
Skin biopsies from patients with psoriasis ( = 6; plaque and non-lesional skin) and healthy controls ( = 6) were incubated with anti-VEGF-A monoclonal antibody (bevacizumab, Avastin®) or a human IgG isotype control for 72-h in serum-free organ culture. CD31/LYVE-1, Ki-67, and mast cell tryptase expression were assessed by quantitative immunohistomorphometry. VEGF-A levels in plasma, PBMCs and skin culture supernatants were measured.
Inhibition of VEGF-A blocked all free VEGF-A ex vivo, reduced blood vessel area and the number of blood vessel endothelial cells in plaques of psoriasis (* < 0.05). The treatment effect correlated significantly with levels of VEGF-A in organ culture supernatants ( = 0.94; * < 0.05) from plaque skin and with plasma levels of VEGF-A from patients with psoriasis ( = 0.943; * = 0.017).
These ex vivo data are the first studies to objectively investigate the potential of VEGF-A inhibition as a novel adjuvant treatment strategy for psoriasis. Taken together, our data encourage further investigation by clinical trial to explore whether downregulating pathological angiogenesis has clinical utility, especially in patients with severe psoriasis or those with elevated levels of VEGF-A in plasma and/or skin.
血管内皮生长因子（VEGF）-A介导的血管生成参与银屑病的发病机制，因此提出了抗VEGF-A治疗可能对银屑病有益的假说。虽然抗血管生成药物已用于肿瘤学和眼科，但这些治疗策略在银屑病管理方面仍未得到探索。
我们的目的是在体外研究VEGF-A阻断对银屑病患者器官培养的斑块和非皮损皮肤中的血管、表皮和免疫细胞的影响。
将银屑病患者（n = 6；斑块和非皮损皮肤）和健康对照者（n = 6）的皮肤活检组织在无血清器官培养中与抗VEGF-A单克隆抗体（贝伐单抗，阿瓦斯汀®）或人IgG同型对照孵育72小时。通过定量免疫组织形态计量学评估CD31/LYVE-1、Ki-67和肥大细胞类胰蛋白酶的表达。测量血浆、外周血单核细胞和皮肤培养上清液中的VEGF-A水平。
体外抑制VEGF-A可阻断所有游离的VEGF-A，减少银屑病斑块中的血管面积和血管内皮细胞数量（*P < 0.05）。治疗效果与斑块皮肤器官培养上清液中VEGF-A的水平（r = 0.94；*P < 0.05）以及银屑病患者血浆中VEGF-A的水平显著相关（r = 0.943；*P = 0.017）。
这些体外数据是首次客观研究VEGF-A抑制作为银屑病新型辅助治疗策略潜力的研究。综上所述，我们的数据鼓励通过临床试验进一步研究，以探索下调病理性血管生成是否具有临床实用性，特别是在重度银屑病患者或血浆和/或皮肤中VEGF-A水平升高的患者中。
