Abstract
Endothelial dysfunction is among the major triggers of cardiovascular disease, also promoting thrombosis, restenosis, and neoatherosclerosis within the conduit and coronary artery upon the coronary artery bypass graft surgery. To recapitulate the paracrine interactions between arterial and venous endothelial cells (ECs) by cross-addition of the conditioned medium to the respective cell cultures. Conditioned (24 hours) serum-free medium from confluent primary human coronary artery ECs (HCAEC), primary human internal thoracic artery ECs (HITAEC) and primary human saphenous vein ECs (HSaVEC) was added to a confluent monolayer of intact HCAEC, HITAEC, and HSaVEC for another 24 hours. Cellular response has been assessed by reverse transcription-quantitative polymerase chain reaction, Western blotting and enzyme-linked immunosorbent assay. Gene expression analysis showed that HITAEC-conditioned medium ameliorated inflammatory response in HCAEC, in contrast to HSaVEC-conditioned medium. In turn, HCAEC-conditioned medium maintained the endothelial phenotype of HITAEC. Further, HCAEC- and HITAEC-conditioned medium stimulated release of pro-angiogenic molecules by intact HCAEC and HSaVEC cultures. HSaVEC-conditioned medium notably reduced the secretion of pro-inflammatory cytokine interleukin-6 in all cell cultures. Conclusions: Paracrine interactions between HITAEC and HCAEC govern their anti-inflammatory status and enhance HCAEC angiogenic potential, partially explaining the higher primary patency of arterial conduits and resistance of coronary artery to thrombosis, restenosis and neoatherosclerosis in the long-term period after total arterial revascularisation.
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Funding
This study was supported by the Complex Program of Basic Research under the Siberian Branch of the Russian Academy of Sciences within the Basic Research Topic of Research Institute for Complex Issues of Cardiovascular Diseases № 0419-2021-001 «Novel anti-atherosclerotic therapies and machine learning solutions for automated diagnosis and prognostication of cardiovascular disease». The study is financially supported by the Ministry of Science and Higher Education of the Russian Federation (National Project Science and Universities).
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Idea of work and planning of the experiment—A.V.F., A.G.K., E.V.G., performing experiment—D.K.S., V.E.M., M.Yu.S., A.V.S., A.O.P., A.Yu.K., data processing—A.G.K., literature analysis—A.Yu.K., V.E.M., A.O.P., N.I.Z., writing and editing the article—A.V.F., V.E.M., A.Yu.K, A.G.K.
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Translated by A. Dyomina
Russian Text © The Author(s), 2022, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2022, Vol. 108, No. 8, pp. 940–956https://doi.org/10.31857/S0869813922080039.
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Frolov, A.V., Shishkova, D.K., Markova, V.E. et al. Paracrine Effects of Conditioned Medium during Its Cross-Addition to Arterial and Venous Endothelial Cells. J Evol Biochem Phys 58, 1180–1192 (2022). https://doi.org/10.1134/S0022093022040214
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DOI: https://doi.org/10.1134/S0022093022040214