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血管生成——未来治疗的新靶点。

Angiogenesis--a new target for future therapy.

作者信息

Pandya Nilesh M, Dhalla Naranjan S, Santani Dev D

机构信息

Department of Pharmacology, C. U. Shah College of Pharmacy and Research, Wadhwan City-363030, Dist. Surendranagar, India.

出版信息

Vascul Pharmacol. 2006 May;44(5):265-74. doi: 10.1016/j.vph.2006.01.005. Epub 2006 Mar 20.

Abstract

Development of blood vessels from in situ differentiating endothelial cells (EC) is called vasculogenesis, whereas sprouting of new blood vessels from the pre-existing ones is termed angiogenesis or neovascularisation. Angiogenesis, the growth of new blood vessels, is essential during tissue repair, foetal development, and female reproductive cycle. In contrast, uncontrolled angiogenesis promotes tumor and retinopathies, while inadequate angiogenesis can lead to coronary artery disease. A balance between pro-angiogenic and anti-angiogenic growth factors and cytokines tightly controls angiogenesis. With the identification of several proangiogenic molecules such as the vascular endothelial cell growth factor (VEGF), the fibroblast growth factors (FGFs), and the angiopoietins, and the recent description of specific inhibitors of angiogenesis such as platelet factor-4, angiostatin, endostatin, and vasostatin, it is recognized that therapeutic interference with vasculature formation offers a tool for clinical applications in various pathologies. Inhibition of angiogenesis can prevent diseases such as cancer, diabetic nephropathy, arthritis, psoriasis, whereas stimulation of angiogenesis is beneficial in the treatment of coronary artery disease (CAD), cardiac failure, tissue injury, etc. One of the most specific and critical regulators of angiogenesis is vascular endothelial growth factor (VEGF), which regulates endothelial proliferation, permeability, and survival. Substantial evidence also implicates VEGF as an angiogenic mediator in tumors and intraocular neovascular syndromes, and numerous clinical trials are presently testing the hypothesis that inhibition of VEGF may have therapeutic value.

摘要

原位分化的内皮细胞(EC)形成血管的过程称为血管生成,而从已有的血管中长出新血管则被称为血管生成或新生血管形成。血管生成,即新血管的生长,在组织修复、胎儿发育和女性生殖周期中至关重要。相反,不受控制的血管生成会促进肿瘤和视网膜病变,而血管生成不足则会导致冠状动脉疾病。促血管生成和抗血管生成生长因子及细胞因子之间的平衡严格控制着血管生成。随着几种促血管生成分子如血管内皮细胞生长因子(VEGF)、成纤维细胞生长因子(FGFs)和血管生成素的发现,以及最近对血管生成特异性抑制剂如血小板因子-4、血管抑素、内皮抑素和血管抑制素的描述,人们认识到对脉管系统形成的治疗性干预为各种病理学的临床应用提供了一种工具。抑制血管生成可以预防癌症、糖尿病肾病、关节炎、牛皮癣等疾病,而刺激血管生成则有利于治疗冠状动脉疾病(CAD)、心力衰竭、组织损伤等。血管内皮生长因子(VEGF)是血管生成最特异性和关键的调节因子之一,它调节内皮细胞的增殖、通透性和存活。大量证据还表明VEGF是肿瘤和眼内新生血管综合征中的血管生成介质,目前许多临床试验正在检验抑制VEGF可能具有治疗价值这一假说。

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