摘要
芽生血管由现有血管的扩张与重塑所组成,新生血管芽相互连接形成新的血管袢。内皮祖细胞(EPCs)是一类具有高增殖潜能,在新生血管形成过程中可分化为成熟的内皮细胞(EC)的干细胞。除了这种直接结构作用,内皮祖细胞(EPCs)增加新生血管内皮祖细胞数量并能分泌多种能够增强成熟内皮细胞和外周祖细胞增殖,存活和功能的促血管生成因子。尽管通过成熟内皮细胞使血管芽生只涉及到内在的内皮细胞,但内皮祖细胞促进血管再生任然面临巨大挑战。动员骨髓内皮祖细胞必须从干细胞生态位分离,内渗进入骨髓血管,达到缺氧区或肿瘤的部位,溢出和纳入新的血管腔,从而补充芽生血管成熟内皮细胞。本文目的在于突出能够控制每一个步骤的主要蛋白酶系统的作用。本文所描述涉及血管芽生时血管形成的关键酶系统包括基质金属蛋白酶(MMPs)、丝氨酸蛋白酶尿激酶型纤维蛋白溶酶原激活质(uPA)及其受体(uPAR)和相关的纤溶酶原及纤溶酶受体、中性粒细胞弹性蛋白酶和组织蛋白酶。通过相关蛋白酶系统的调节,血管再生不管在生理还是病理过程如肿瘤,内皮祖细胞对血管再生过程的控制都起着关键作用,这为病理性血管再生的有效控制治的疗前景提供了新的机遇。
关键词: 血管再生,组织蛋白酶,内皮祖细胞(EPCs),基质金属蛋白酶(MMPs),蛋白酶,uPA/uPAR
Current Molecular Medicine
Title:Endothelial Progenitor Cells in Sprouting Angiogenesis: Proteases Pave the Way
Volume: 15 Issue: 7
Author(s): A. Laurenzana, G. Fibbi, F. Margheri, A. Biagioni, C. Luciani, M. Del Rosso and A. Chilla
Affiliation:
关键词: 血管再生,组织蛋白酶,内皮祖细胞(EPCs),基质金属蛋白酶(MMPs),蛋白酶,uPA/uPAR
摘要: Sprouting angiogenesis consists of the expansion and remodelling of existing vessels, where the vascular sprouts connect each other to form new vascular loops. Endothelial Progenitor Cells (EPCs) are a subtype of stem cells, with high proliferative potential, able to differentiate into mature Endothelial Cells (ECs) during the neovascularization process. In addition to this direct structural role EPCs improve neovascularization, also secreting numerous pro-angiogenic factors able to enhance the proliferation, survival and function of mature ECs, and other surrounding progenitor cells. While sprouting angiogenesis by mature ECs involves resident ECs, the vasculogenic contribution of EPCs is a high hurdle race. Bone marrowmobilized EPCs have to detach from the stem cell niche, intravasate into bone marrow vessels, reach the hypoxic area or tumour site, extravasate and incorporate into the new vessel lumen, thus complementing the resident mature ECs in sprouting angiogenesis. The goal of this review is to highlight the role of the main protease systems able to control each of these steps. The pivotal protease systems here described, involved in vascular patterning in sprouting angiogenesis, are the matrix-metalloproteinases (MMPs), the serineproteinases urokinase-type plasminogen activator (uPA) associated with its receptor (uPAR) and receptorassociated plasminogen/plasmin, the neutrophil elastase and the cathepsins. Since angiogenesis plays a critical role not only in physiological but also in pathological processes, such as in tumours, controlling the contribution of EPCs to the angiogenic process, through the regulation of the protease systems involved, could yield new opportunities for the therapeutic prospect of efficient control of pathological angiogenesis.
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A. Laurenzana, G. Fibbi, F. Margheri, A. Biagioni, C. Luciani, M. Del Rosso and A. Chilla , Endothelial Progenitor Cells in Sprouting Angiogenesis: Proteases Pave the Way, Current Molecular Medicine 2015; 15 (7) . https://dx.doi.org/10.2174/1566524015666150831131214
DOI https://dx.doi.org/10.2174/1566524015666150831131214 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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