Paracrine Effects of Conditioned Medium during Its Cross-Addition to Arterial and Venous Endothelial Cells

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.