2014年7月5日訊 /生物谷BIOON/--血管新生對於身體的發育是必不可少的。隨著器官生長，血管網絡必須「養活」新細胞及消除廢物。但是，相同的過程在許多癌症的發生和進展中也起著的關鍵作用，因為它允許腫瘤的快速增長。
隨著抑制和加速新血管生成的相關運用，需要更基本的了解什麼樣來調節血管生成。現在，賓夕法尼亞州波士頓大學和哈佛大學研究人員已經發現當血液流經血管壁時，有一種閾值的存在，在引起新毛細血管發芽中發揮作用。這一發現可能有助於為抗癌藥物開發鋪平道路。他們的研究結果發表在PNAS雜誌上。
該小組的實驗使用「單晶片上的血管」（blood-vessel-on-a-chip）設備，使用微流體技術來模擬正常深層組織內發生的過程（血管發生過程）。他們發現，一旦流體流經血管生成的力超過一定的閾值，人工血管裡的細胞會發芽，形成新的血管。
研究人員解釋說：也許我們有一天可以利用此，增強特定情況下如心臟發作後的血管再生。在他們的實驗中，研究控制人工血管內的流體流動，通過改變部署在血管中薄針的形狀和朝向，引發新的血管會發芽。使用數學模型，他們預測了人工血管中超過出芽閾值的確切點，從而查明新血管將形成的位置。
現在，研究人員的目標是推進新實驗，旨在弄清楚細胞如何感知這個機械閾值。下一個步驟是確定這種現象背後的分子機制，Galie說：弄清楚什麼蛋白質參與其中，以及如何可能對其進行靶向作用。（生物谷Bioon.com）
Fluid shear stress threshold regulates angiogenic sprouting
Peter A. Galie,et al.
The density and architecture of capillary beds that form within a tissue depend on many factors, including local metabolic demand and blood flow. Here, using microfluidic control of local fluid mechanics, we show the existence of a previously unappreciated flow-induced shear stress threshold that triggers angiogenic sprouting. Both intraluminal shear stress over the endothelium and transmural flow through the endothelium above 10 dyn/cm2 triggered endothelial cells to sprout and invade into the underlying matrix, and this threshold is not impacted by the maturation of cell–cell junctions or pressure gradient across the monolayer. Antagonizing VE-cadherin widened cell–cell junctions and reduced the applied shear stress for a given transmural flow rate, but did not affect the shear threshold for sprouting. Furthermore, both transmural and luminal flow induced expression of matrix metalloproteinase 1, and this up-regulation was required for the flow-induced sprouting. Once sprouting was initiated, continuous flow was needed to both sustain sprouting and prevent retraction. To explore the potential ramifications of a shear threshold on the spatial patterning of new sprouts, we used finite-element modeling to predict fluid shear in a variety of geometric settings and then experimentally demonstrated that transmural flow guided preferential sprouting toward paths of draining interstitial fluid flow as might occur to connect capillary beds to venules or lymphatics. In addition, we show that luminal shear increases in local narrowings of vessels to trigger sprouting, perhaps ultimately to normalize shear stress across the vasculature. Together, these studies highlight the role of shear stress in controlling angiogenic sprouting and offer a potential homeostatic mechanism for regulating vascular density.