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[血管内皮生长因子在血管生成及糖尿病视网膜病变中的作用]

[The role of vascular endothelial growth factor in angiogenesis and diabetic retinopathy].

作者信息

Valiatti Fabiana Borba, Crispim Daisy, Benfica Camila, Valiatti Bruna Borba, Kramer Caroline K, Canani Luís Henrique

机构信息

Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.

出版信息

Arq Bras Endocrinol Metabol. 2011 Mar;55(2):106-13. doi: 10.1590/S0004-27302011000200002.

Abstract

Diabetic retinopathy (DR), a DM microvascular complication, is the leading cause of blindness. Angiogenic factors such as vascular endothelial growth factor (VEGF) are involved in the pathogenesis of DR. VEGF-A is a potent, multifunctional cytokine that acts through the receptors VEGFR-1 and VEGFR-2 expressed in the vascular endothelium and causing increased vascular permeability and neovascularization stimulation in both physiological and pathological processes. The expression of VEGFR-1 is upregulated by hypoxia and is less responsive to VEGF compared to VEGFR-2 which is the main mediator mitogenic, angiogenic, and increased vascular permeability. VEGF polymorphisms have been studied in DR susceptibility and progression. Significant association between the polymorphism 634C / G and the presence of RD is reported mainly in relation to allele C. The homozygous CC is associated to proliferative RD and to increased vitreous and serum levels of VEGF suggesting that the presence of the C allele is an independent risk factor for RD. The knowledge of VEGF lead to the development of anti-VEGF drugs (pegaptanib, ranibizumab and bevacizumab) aiming to prevent pathological neovascularization. The anti-VEGF therapy is a reality in practice medical treatment of DR.

摘要

糖尿病视网膜病变(DR)是糖尿病的一种微血管并发症,是导致失明的主要原因。血管内皮生长因子(VEGF)等血管生成因子参与了DR的发病机制。VEGF-A是一种强效的多功能细胞因子,通过血管内皮中表达的受体VEGFR-1和VEGFR-2发挥作用,在生理和病理过程中均可导致血管通透性增加和刺激新生血管形成。VEGFR-1的表达受缺氧上调,与主要介导有丝分裂、血管生成和血管通透性增加的VEGFR-2相比,对VEGF的反应性较低。VEGF基因多态性已在DR易感性和病情进展方面进行了研究。主要报道了634C/G多态性与增殖性糖尿病视网膜病变(RD)的存在之间存在显著关联,主要与等位基因C有关。纯合子CC与增殖性RD以及玻璃体和血清VEGF水平升高相关,这表明C等位基因的存在是RD的一个独立危险因素。对VEGF的认识促使了旨在预防病理性新生血管形成的抗VEGF药物(哌加他尼、雷珠单抗和贝伐单抗)的研发。抗VEGF治疗在DR的实际医疗中已成为现实。

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