Endothelial damage inhibitor preserves the integrity of venous endothelial cells from patients undergoing coronary bypass surgery

Abstract OBJECTIVES Despite the success of coronary artery bypass graft (CABG) surgery using autologous saphenous vein grafts (SVGs), nearly 50% of patients experience vein graft disease within 10 years of surgery. One contributing factor to early vein graft disease is endothelial damage during shor...

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Veröffentlicht in:European journal of cardio-thoracic surgery 2023-12, Vol.64 (6)
Hauptverfasser: Nazari-Shafti, Timo Z, Thau, Henriette, Zacharova, Ema, Beez, Christien M, Exarchos, Vasileios, Neuber, Sebastian, Meyborg, Heike, Puhl, Kerstin, Wittig, Corey, Szulcek, Robert, Neumann, Konrad, Giampietro, Costanza, Krüger, Katrin, Cesarovic, Nikola, Falk, Volkmar, Caliskan, Etem, Rodriguez Cetina Biefer, Hector, Emmert, Maximilian Y
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container_issue 6
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container_title European journal of cardio-thoracic surgery
container_volume 64
creator Nazari-Shafti, Timo Z
Thau, Henriette
Zacharova, Ema
Beez, Christien M
Exarchos, Vasileios
Neuber, Sebastian
Meyborg, Heike
Puhl, Kerstin
Wittig, Corey
Szulcek, Robert
Neumann, Konrad
Giampietro, Costanza
Krüger, Katrin
Cesarovic, Nikola
Falk, Volkmar
Caliskan, Etem
Rodriguez Cetina Biefer, Hector
Emmert, Maximilian Y
description Abstract OBJECTIVES Despite the success of coronary artery bypass graft (CABG) surgery using autologous saphenous vein grafts (SVGs), nearly 50% of patients experience vein graft disease within 10 years of surgery. One contributing factor to early vein graft disease is endothelial damage during short-term storage of SVGs in inappropriate solutions. Our aim was to evaluate the effects of a novel endothelial damage inhibitor (EDI) on SVGs from patients undergoing elective CABG surgery and on venous endothelial cells (VECs) derived from these SVGs. METHODS SVGs from 11 patients participating in an ongoing clinical registry (NCT02922088) were included in this study, and incubated with both full electrolyte solution (FES) or EDI for 1 h and then examined histologically. In 8 of 11 patients, VECs were isolated from untreated grafts, incubated with both FES and EDI for 2 h under hypothermic stress conditions and then analysed for activation of an inflammatory phenotype, cell damage and cytotoxicity, as well as endothelial integrity and barrier function. RESULTS The EDI was superior to FES in protecting the endothelium in SVGs (74 ± 8% versus 56 ± 8%, P 
doi_str_mv 10.1093/ejcts/ezad327
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One contributing factor to early vein graft disease is endothelial damage during short-term storage of SVGs in inappropriate solutions. Our aim was to evaluate the effects of a novel endothelial damage inhibitor (EDI) on SVGs from patients undergoing elective CABG surgery and on venous endothelial cells (VECs) derived from these SVGs. METHODS SVGs from 11 patients participating in an ongoing clinical registry (NCT02922088) were included in this study, and incubated with both full electrolyte solution (FES) or EDI for 1 h and then examined histologically. In 8 of 11 patients, VECs were isolated from untreated grafts, incubated with both FES and EDI for 2 h under hypothermic stress conditions and then analysed for activation of an inflammatory phenotype, cell damage and cytotoxicity, as well as endothelial integrity and barrier function. RESULTS The EDI was superior to FES in protecting the endothelium in SVGs (74 ± 8% versus 56 ± 8%, P &lt; 0.001). Besides confirming that the EDI prevents apoptosis in SVG-derived VECs, we also showed that the EDI temporarily reduces adherens junctions in VECs while protecting focal adhesions compared to FES. CONCLUSIONS The EDI protects the connectivity and function of the SVG endothelium. Our data suggest that the EDI can preserve focal adhesions in VECs during short-term storage after graft harvesting. This might explain the superiority of the EDI in maintaining most of the endothelium in venous CABG surgery conduits. Coronary artery bypass grafting (CABG) with saphenous vein grafts (SVGs) remains the preferred treatment for patients with complex multivessel coronary artery disease, despite the availability of multi and total arterial approaches [1, 2].</description><identifier>ISSN: 1873-734X</identifier><identifier>EISSN: 1873-734X</identifier><identifier>DOI: 10.1093/ejcts/ezad327</identifier><identifier>PMID: 37740952</identifier><language>eng</language><publisher>Germany: Oxford University Press</publisher><subject>Coronary Artery Bypass - adverse effects ; Endothelial Cells ; Endothelium, Vascular ; Humans ; Saphenous Vein - transplantation ; Vascular Diseases ; Vascular Patency - physiology</subject><ispartof>European journal of cardio-thoracic surgery, 2023-12, Vol.64 (6)</ispartof><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. 2023</rights><rights>The Author(s) 2023. 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All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-a2dc4bd105817baffe072818b5497b957d577b375c46d2d271735dda20e179063</citedby><cites>FETCH-LOGICAL-c365t-a2dc4bd105817baffe072818b5497b957d577b375c46d2d271735dda20e179063</cites><orcidid>0000-0003-1833-8440 ; 0000-0002-9055-6891 ; 0000-0002-9051-7841 ; 0000-0003-1373-636X ; 0000-0002-7911-8620</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37740952$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nazari-Shafti, Timo Z</creatorcontrib><creatorcontrib>Thau, Henriette</creatorcontrib><creatorcontrib>Zacharova, Ema</creatorcontrib><creatorcontrib>Beez, Christien M</creatorcontrib><creatorcontrib>Exarchos, Vasileios</creatorcontrib><creatorcontrib>Neuber, Sebastian</creatorcontrib><creatorcontrib>Meyborg, Heike</creatorcontrib><creatorcontrib>Puhl, Kerstin</creatorcontrib><creatorcontrib>Wittig, Corey</creatorcontrib><creatorcontrib>Szulcek, Robert</creatorcontrib><creatorcontrib>Neumann, Konrad</creatorcontrib><creatorcontrib>Giampietro, Costanza</creatorcontrib><creatorcontrib>Krüger, Katrin</creatorcontrib><creatorcontrib>Cesarovic, Nikola</creatorcontrib><creatorcontrib>Falk, Volkmar</creatorcontrib><creatorcontrib>Caliskan, Etem</creatorcontrib><creatorcontrib>Rodriguez Cetina Biefer, Hector</creatorcontrib><creatorcontrib>Emmert, Maximilian Y</creatorcontrib><title>Endothelial damage inhibitor preserves the integrity of venous endothelial cells from patients undergoing coronary bypass surgery</title><title>European journal of cardio-thoracic surgery</title><addtitle>Eur J Cardiothorac Surg</addtitle><description>Abstract OBJECTIVES Despite the success of coronary artery bypass graft (CABG) surgery using autologous saphenous vein grafts (SVGs), nearly 50% of patients experience vein graft disease within 10 years of surgery. One contributing factor to early vein graft disease is endothelial damage during short-term storage of SVGs in inappropriate solutions. Our aim was to evaluate the effects of a novel endothelial damage inhibitor (EDI) on SVGs from patients undergoing elective CABG surgery and on venous endothelial cells (VECs) derived from these SVGs. METHODS SVGs from 11 patients participating in an ongoing clinical registry (NCT02922088) were included in this study, and incubated with both full electrolyte solution (FES) or EDI for 1 h and then examined histologically. In 8 of 11 patients, VECs were isolated from untreated grafts, incubated with both FES and EDI for 2 h under hypothermic stress conditions and then analysed for activation of an inflammatory phenotype, cell damage and cytotoxicity, as well as endothelial integrity and barrier function. RESULTS The EDI was superior to FES in protecting the endothelium in SVGs (74 ± 8% versus 56 ± 8%, P &lt; 0.001). Besides confirming that the EDI prevents apoptosis in SVG-derived VECs, we also showed that the EDI temporarily reduces adherens junctions in VECs while protecting focal adhesions compared to FES. CONCLUSIONS The EDI protects the connectivity and function of the SVG endothelium. Our data suggest that the EDI can preserve focal adhesions in VECs during short-term storage after graft harvesting. This might explain the superiority of the EDI in maintaining most of the endothelium in venous CABG surgery conduits. Coronary artery bypass grafting (CABG) with saphenous vein grafts (SVGs) remains the preferred treatment for patients with complex multivessel coronary artery disease, despite the availability of multi and total arterial approaches [1, 2].</description><subject>Coronary Artery Bypass - adverse effects</subject><subject>Endothelial Cells</subject><subject>Endothelium, Vascular</subject><subject>Humans</subject><subject>Saphenous Vein - transplantation</subject><subject>Vascular Diseases</subject><subject>Vascular Patency - physiology</subject><issn>1873-734X</issn><issn>1873-734X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkL1PwzAQxS0EoqUwsiKPLAHb-XAyoqp8SJVYQGKLnPiSukriYDuVwsZ_jksLdGO60-l37949hC4puaEkC29hXTp7Cx9ChowfoSlNeRjwMHo7Pugn6MzaNSEk8dApmoScRySL2RR9Ljqp3QoaJRosRStqwKpbqUI5bXBvwILZgMUe8XMHtVFuxLrCG-j0YDEcrJfQNBZXRre4F05B5yweOgmm1qqrcamN7oQZcTH2wlpsB1ODGc_RSSUaCxf7OkOv94uX-WOwfH54mt8tgzJMYhcIJsuokJTEKeWFqCognKU0LeIo40UWcxlzXoQ8LqNEMsk45WEspWAEKM_84zN0vdPtjX4fwLq8VXZrWXTgP8lZmqSURUnEPRrs0NJoaw1UeW9U663nlOTb1PPv1PN96p6_2ksPRQvyl_6J-e-2Hvp_tL4AL1qRUg</recordid><startdate>20231201</startdate><enddate>20231201</enddate><creator>Nazari-Shafti, Timo Z</creator><creator>Thau, Henriette</creator><creator>Zacharova, Ema</creator><creator>Beez, Christien M</creator><creator>Exarchos, Vasileios</creator><creator>Neuber, Sebastian</creator><creator>Meyborg, Heike</creator><creator>Puhl, Kerstin</creator><creator>Wittig, Corey</creator><creator>Szulcek, Robert</creator><creator>Neumann, Konrad</creator><creator>Giampietro, Costanza</creator><creator>Krüger, Katrin</creator><creator>Cesarovic, Nikola</creator><creator>Falk, Volkmar</creator><creator>Caliskan, Etem</creator><creator>Rodriguez Cetina Biefer, Hector</creator><creator>Emmert, Maximilian Y</creator><general>Oxford University Press</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/0000-0003-1833-8440</orcidid><orcidid>https://orcid.org/0000-0002-9055-6891</orcidid><orcidid>https://orcid.org/0000-0002-9051-7841</orcidid><orcidid>https://orcid.org/0000-0003-1373-636X</orcidid><orcidid>https://orcid.org/0000-0002-7911-8620</orcidid></search><sort><creationdate>20231201</creationdate><title>Endothelial damage inhibitor preserves the integrity of venous endothelial cells from patients undergoing coronary bypass surgery</title><author>Nazari-Shafti, Timo Z ; 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One contributing factor to early vein graft disease is endothelial damage during short-term storage of SVGs in inappropriate solutions. Our aim was to evaluate the effects of a novel endothelial damage inhibitor (EDI) on SVGs from patients undergoing elective CABG surgery and on venous endothelial cells (VECs) derived from these SVGs. METHODS SVGs from 11 patients participating in an ongoing clinical registry (NCT02922088) were included in this study, and incubated with both full electrolyte solution (FES) or EDI for 1 h and then examined histologically. In 8 of 11 patients, VECs were isolated from untreated grafts, incubated with both FES and EDI for 2 h under hypothermic stress conditions and then analysed for activation of an inflammatory phenotype, cell damage and cytotoxicity, as well as endothelial integrity and barrier function. RESULTS The EDI was superior to FES in protecting the endothelium in SVGs (74 ± 8% versus 56 ± 8%, P &lt; 0.001). Besides confirming that the EDI prevents apoptosis in SVG-derived VECs, we also showed that the EDI temporarily reduces adherens junctions in VECs while protecting focal adhesions compared to FES. CONCLUSIONS The EDI protects the connectivity and function of the SVG endothelium. Our data suggest that the EDI can preserve focal adhesions in VECs during short-term storage after graft harvesting. This might explain the superiority of the EDI in maintaining most of the endothelium in venous CABG surgery conduits. Coronary artery bypass grafting (CABG) with saphenous vein grafts (SVGs) remains the preferred treatment for patients with complex multivessel coronary artery disease, despite the availability of multi and total arterial approaches [1, 2].</abstract><cop>Germany</cop><pub>Oxford University Press</pub><pmid>37740952</pmid><doi>10.1093/ejcts/ezad327</doi><orcidid>https://orcid.org/0000-0003-1833-8440</orcidid><orcidid>https://orcid.org/0000-0002-9055-6891</orcidid><orcidid>https://orcid.org/0000-0002-9051-7841</orcidid><orcidid>https://orcid.org/0000-0003-1373-636X</orcidid><orcidid>https://orcid.org/0000-0002-7911-8620</orcidid><oa>free_for_read</oa></addata></record>
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source Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
subjects Coronary Artery Bypass - adverse effects
Endothelial Cells
Endothelium, Vascular
Humans
Saphenous Vein - transplantation
Vascular Diseases
Vascular Patency - physiology
title Endothelial damage inhibitor preserves the integrity of venous endothelial cells from patients undergoing coronary bypass surgery
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