Kirkpatrick Nathaniel D, Andreou Stylianos, Hoying James B, Utzinger Urs
University of Arizona, Division of Biomedical Engineering, Tucson, AZ, USA.
Am J Physiol Heart Circ Physiol. 2007 Jun;292(6):H3198-206. doi: 10.1152/ajpheart.01234.2006. Epub 2007 Feb 16.
To better understand interstitial matrix remodeling during angiogenesis, we probed endogenous optical signatures of collagen fibrils and cells with multiphoton microscopy to noninvasively visualize, in real-time, changes to fibril organization around angiogenic sprouts and growing neovessels. From analyses of the second-harmonic generation signal from fibrillar collagen and two-photon excited fluorescence, as well as coherent transmitted light from vascular cells, we found that microvessel fragments interacting with the collagen matrix exhibited two key features: a strong association of fibrillar collagen around the parent vessel fragment during vessel construct reconstitution and a substantial collagen fibril reorganization by sprout and neovessel tips. Results indicate that angiogenic sprouts and growing neovessels actively and differentially remodel existing collagen fibrils. This imaging approach to assess local changes in matrix organization may have a broader impact on tissue biology and mechanics during angiogenesis and allow for new insights in cardiovascular, diabetes, and cancer research.
为了更好地理解血管生成过程中的间质基质重塑，我们用多光子显微镜探测了胶原纤维和细胞的内源性光学信号，以实时、无创地可视化血管生成芽和新生血管周围纤维组织的变化。通过对纤维状胶原的二次谐波信号、双光子激发荧光以及血管细胞的相干透射光进行分析，我们发现与胶原基质相互作用的微血管片段呈现出两个关键特征：在血管构建重建过程中，纤维状胶原在母血管片段周围强烈聚集；芽和新生血管尖端对胶原纤维进行大量重组。结果表明，血管生成芽和新生血管会主动且不同程度地重塑现有的胶原纤维。这种评估基质组织局部变化的成像方法可能会对血管生成过程中的组织生物学和力学产生更广泛的影响，并为心血管、糖尿病和癌症研究带来新的见解。
