Department of Mechanical Engineering, Seoul National University, Seoul 08826, Republic of Korea.
Interdisciplinary Program in Bioengineering, Seoul National University, Seoul 08826, Republic of Korea.
ACS Nano. 2024 Sep 10;18(36):24909-24928. doi: 10.1021/acsnano.4c05537. Epub 2024 Aug 29.
This research introduces a vascular phenotypic and proteomic analysis (VPT) platform designed to perform high-throughput experiments on vascular development. The VPT platform utilizes an open-channel configuration that facilitates angiogenesis by precise alignment of endothelial cells, allowing for a 3D morphological examination and protein analysis. We study the effects of antiangiogenic agents─bevacizumab, ramucirumab, cabozantinib, regorafenib, wortmannin, chloroquine, and paclitaxel─on cytoskeletal integrity and angiogenic sprouting, observing an approximately 50% reduction in sprouting at higher drug concentrations. Precise LC-MS/MS analyses reveal global protein expression changes in response to four of these drugs, providing insights into the signaling pathways related to the cell cycle, cytoskeleton, cellular senescence, and angiogenesis. Our findings emphasize the intricate relationship between cytoskeletal alterations and angiogenic responses, underlining the significance of integrating morphological and proteomic data for a comprehensive understanding of angiogenesis. The VPT platform not only advances our understanding of drug impacts on vascular biology but also offers a versatile tool for analyzing proteome and morphological features across various models beyond blood vessels.
本研究介绍了一种血管表型和蛋白质组学分析（VPT）平台，旨在对血管发育进行高通量实验。VPT 平台采用开放式通道配置，通过精确对准内皮细胞促进血管生成，从而实现 3D 形态检查和蛋白质分析。我们研究了抗血管生成剂——贝伐单抗、雷莫芦单抗、卡博替尼、瑞戈非尼、渥曼青霉素、氯喹和紫杉醇——对细胞骨架完整性和血管生成发芽的影响，在较高药物浓度下观察到发芽减少约 50%。精确的 LC-MS/MS 分析揭示了这四种药物对整体蛋白质表达的影响，为与细胞周期、细胞骨架、细胞衰老和血管生成相关的信号通路提供了深入了解。我们的研究结果强调了细胞骨架改变与血管生成反应之间的复杂关系，突出了整合形态和蛋白质组学数据以全面了解血管生成的重要性。VPT 平台不仅推进了我们对药物对血管生物学影响的理解，还为分析除血管以外的各种模型的蛋白质组和形态特征提供了一种多功能工具。
