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

Robert Szulcek, Maximilian Y Emmert, Hector Rodriguez Cetina Biefer, Etem Caliskan, Volkmar Falk, Nikola Cesarovic, Katrin Krüger, Costanza Giampietro, Konrad Neumann, Timo Z Nazari-Shafti, Corey Wittig, Kerstin Puhl, Heike Meyborg, Sebastian Neuber, Vasileios Exarchos, Christien M Beez, Ema Zacharova, Henriette Thau

Journal: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 2023;64(6):ezad327

PMID: 37740952

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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 < 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.

Address: Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum der Charité (DHZC), Berlin, Germany.; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; Berlin Institute of Health at Charité-Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany.; German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany.; Department of Life Sciences, IMC University of Applied Sciences Krems, Krems an der Donau, Austria.; Department of Cardiac Anesthesiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité (DHZC), Berlin, Germany.; Laboratory for in vitro modeling systems of pulmonary and thrombotic diseases, Institute of Physiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.; Institute of Biometry and Clinical Epidemiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.; Experimental Continuum Mechanics, Empa Swiss Federal Laboratories for Materials Science and Technology, Dübendorf, Switzerland.; Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Department of Cardiac Surgery, City Hospital of Zurich, Site Triemli, Zurich, Switzerland.; Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland.

DOI: 10.1093/ejcts/ezad327

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MeSH Terms: Humans, Endothelial Cells, Saphenous Vein, Vascular Patency, Coronary Artery Bypass, Endothelium, Vascular, Vascular Diseases