Inhibition of neovascularization by environmental agents
Inhibition of neovascularization by environmental agents
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DOI：
10.1385/ct:5:2:215
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发表时间：
2005-01-01
影响因子：
3.2
通讯作者：
Walker, MK
中科院分区：
文献类型：
--
作者：
Ivnitski-Steele, I;Walker, MK
新血管的形成，即新生血管，通过两个独特的过程发生：血管生成，即血管母细胞前体血管的从头组装，以及血管生成，即从已存在的血管形成新的毛细血管芽。有许多潜在的靶点，环境污染物可以通过它来抑制新生血管，因此有许多可能的表型结果。已被证明抑制新生血管的两种环境污染物包括2，3，7，8-四氯二苯并对二恶英(TCDD)，一种典型的卤代芳香烃，以及在环境烟草烟雾中发现的成分。研究表明，TCDD通过抑制血管生成刺激的表达以及降低内皮细胞对这些刺激的反应性来破坏新的血管生成。此外，研究表明，环境烟草烟雾的成分，包括吡啶和吡嗪衍生物，可以有效地抑制分支的血管生成过程以及与毛细血管丛形成有关的血管生成过程。此外，TCDD或环境烟草烟雾成分对新生血管的抑制与内皮细胞增殖减少和细胞外基质蛋白表达改变有关。未来的研究将确定被这些污染物扰乱的特定血管生成信号通路，这将提高我们评估它们对人类健康风险的能力。最后，许多其他环境污染物可能会影响新生血管；然而，很少有人对其进行足够详细的研究。因此，还需要更多的研究来确定那些通过破坏新生血管来调节其毒性的环境因子。
The formation of new blood vessels, neovascularization, occurs by two unique processes: vasculogenesis, the de novo assembly of blood vessels from angioblast precursors, and angiogenesis, the formation of new capillary sprouts from pre-existing vessels. There are many potential targets by which environmental pollutants may inhibit neovascularization and thus there are many possible phenotypic outcomes. Two examples of environmental pollutants that have been demonstrated to inhibit neovascularization include 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a prototypical halogenated aromatic hydrocarbon, and constituents found in environmental tobacco smoke. Studies have shown that TCDD disrupts neoangiogenesis by inhibiting the expression of angiogenic stimuli as well as by reducing the responsiveness of endothelial cells to those Stimuli. Additionally, studies have shown that constituents of environmental tobacco smoke, including pyradine and pyrazine derivatives, can potently inhibit the angiogenic process of branching as well as the vasculogenic process involved in capillary plexus formation. Further, the inhibition of neovascularization by either TCDD or environmental tobacco smoke constituents is associated with reduced endothelial cell proliferation and altered expression of extracellular matrix proteins. Future research that identifies the specific angiogenic signaling pathways that are disrupted by these pollutants will improve our ability to assess their risk to human health. Finally, it is likely that many other environmental pollutants impact neovascularization; however, very few have been studied in sufficient detail. Thus, additional research also is needed to identify those environmental agents that mediate their toxicity by disrupting neovascularization.