Integrating Vascular Phenotypic and Proteomic Analysis in an Open Microfluidic Platform
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...
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Veröffentlicht in: | ACS nano 2024-09, Vol.18 (36), p.24909-24928 |
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creator | Jung, Sangmin Cheong, Sunghun Lee, Yoonho Lee, Jungseub Lee, Jihye Kwon, Min-Seok Oh, Young Sun Kim, Taewan Ha, Sungjae Kim, Sung Jae Jo, Dong Hyun Ko, Jihoon Jeon, Noo Li |
description | 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 agentsbevacizumab, ramucirumab, cabozantinib, regorafenib, wortmannin, chloroquine, and paclitaxelon 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. |
doi_str_mv | 10.1021/acsnano.4c05537 |
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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 agentsbevacizumab, ramucirumab, cabozantinib, regorafenib, wortmannin, chloroquine, and paclitaxelon 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.</description><identifier>ISSN: 1936-0851</identifier><identifier>ISSN: 1936-086X</identifier><identifier>EISSN: 1936-086X</identifier><identifier>DOI: 10.1021/acsnano.4c05537</identifier><identifier>PMID: 39208278</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Angiogenesis Inhibitors - chemistry ; Angiogenesis Inhibitors - pharmacology ; Human Umbilical Vein Endothelial Cells - drug effects ; Human Umbilical Vein Endothelial Cells - metabolism ; Humans ; Neovascularization, Physiologic - drug effects ; Phenotype ; Proteomics</subject><ispartof>ACS nano, 2024-09, Vol.18 (36), p.24909-24928</ispartof><rights>2024 The Authors. Published by American Chemical Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-a258t-ac27f6ecf48219030b9b66c77f3f4dc69fd1aac5bf8b59edf8c4a440e17a44fc3</cites><orcidid>0000-0002-6320-6829 ; 0009-0007-8143-8432 ; 0009-0005-6512-7939 ; 0000-0003-0490-3592 ; 0000-0002-8622-1765</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acsnano.4c05537$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acsnano.4c05537$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39208278$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jung, Sangmin</creatorcontrib><creatorcontrib>Cheong, Sunghun</creatorcontrib><creatorcontrib>Lee, Yoonho</creatorcontrib><creatorcontrib>Lee, Jungseub</creatorcontrib><creatorcontrib>Lee, Jihye</creatorcontrib><creatorcontrib>Kwon, Min-Seok</creatorcontrib><creatorcontrib>Oh, Young Sun</creatorcontrib><creatorcontrib>Kim, Taewan</creatorcontrib><creatorcontrib>Ha, Sungjae</creatorcontrib><creatorcontrib>Kim, Sung Jae</creatorcontrib><creatorcontrib>Jo, Dong Hyun</creatorcontrib><creatorcontrib>Ko, Jihoon</creatorcontrib><creatorcontrib>Jeon, Noo Li</creatorcontrib><title>Integrating Vascular Phenotypic and Proteomic Analysis in an Open Microfluidic Platform</title><title>ACS nano</title><addtitle>ACS Nano</addtitle><description>This research introduces a vascular phenotypic and proteomic analysis (VPT) platform designed to perform high-throughput experiments on vascular development. 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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.</description><subject>Angiogenesis Inhibitors - chemistry</subject><subject>Angiogenesis Inhibitors - pharmacology</subject><subject>Human Umbilical Vein Endothelial Cells - drug effects</subject><subject>Human Umbilical Vein Endothelial Cells - metabolism</subject><subject>Humans</subject><subject>Neovascularization, Physiologic - drug effects</subject><subject>Phenotype</subject><subject>Proteomics</subject><issn>1936-0851</issn><issn>1936-086X</issn><issn>1936-086X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kLtPwzAQhy0EoqUws6GMSCitnZftsap4SUXtwGuzLo5dUiV2sZOh_z1GDd2Y7k733U-nD6FrgqcEJ2QG0hswdppJnOcpPUFjwtMixqz4PD32ORmhC--3GOeU0eIcjVKeYJZQNkYfz6ZTGwddbTbRO3jZN-Ci9ZcyttvvahmBqaK1s52ybZjmBpq9r31Um7CJVjtlopdaOqubvq4CsG6g09a1l-hMQ-PV1VAn6O3h_nXxFC9Xj8-L-TKGJGddDDKhulBSZywhHKe45GVRSEp1qrNKFlxXBEDmpWZlzlWlmcwgy7AiNBQt0wm6PeTunP3ule9EW3upmgaMsr0XKeaccs54EtDZAQ3veu-UFjtXt-D2gmDxa1MMNsVgM1zcDOF92arqyP_pC8DdAQiXYmt7F_T4f-N-AAJ0gkM</recordid><startdate>20240910</startdate><enddate>20240910</enddate><creator>Jung, Sangmin</creator><creator>Cheong, Sunghun</creator><creator>Lee, Yoonho</creator><creator>Lee, Jungseub</creator><creator>Lee, Jihye</creator><creator>Kwon, Min-Seok</creator><creator>Oh, Young Sun</creator><creator>Kim, Taewan</creator><creator>Ha, Sungjae</creator><creator>Kim, Sung Jae</creator><creator>Jo, Dong Hyun</creator><creator>Ko, Jihoon</creator><creator>Jeon, Noo Li</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6320-6829</orcidid><orcidid>https://orcid.org/0009-0007-8143-8432</orcidid><orcidid>https://orcid.org/0009-0005-6512-7939</orcidid><orcidid>https://orcid.org/0000-0003-0490-3592</orcidid><orcidid>https://orcid.org/0000-0002-8622-1765</orcidid></search><sort><creationdate>20240910</creationdate><title>Integrating Vascular Phenotypic and Proteomic Analysis in an Open Microfluidic Platform</title><author>Jung, Sangmin ; 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subjects | Angiogenesis Inhibitors - chemistry Angiogenesis Inhibitors - pharmacology Human Umbilical Vein Endothelial Cells - drug effects Human Umbilical Vein Endothelial Cells - metabolism Humans Neovascularization, Physiologic - drug effects Phenotype Proteomics |
title | Integrating Vascular Phenotypic and Proteomic Analysis in an Open Microfluidic Platform |
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