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Published on: January 28, 2020
Release of soluble vascular endothelial growth factor receptor-1 (sFlt-1) during coronary artery bypass surgery
Yves Denizot1, Alexandre Leguyader, Elisabeth Cornu
1UMR CNRS 6101, Centre National de Recherche Scientifique, Université de Limoges, France. yves.denizot@unilim.fr
Insights
Soluble Flt-1 (sFlt-1) significantly increases during coronary artery bypass graft (CABG) surgery with extracorporeal circulation (ECC). This release may contribute to post-CABG complications by affecting vascular endothelial growth factor (VEGF) signaling.
Area of Science:
- Cardiovascular Surgery
- Vascular Biology
- Biochemistry
Background:
- Coronary artery bypass graft (CABG) surgery with extracorporeal circulation (ECC) involves complex physiological changes.
- Soluble forms of vascular endothelial growth factor (VEGF) receptors, specifically sFlt-1 and sKDR, are implicated in vascular regulation.
Purpose of the Study:
- To investigate the plasma concentrations of sFlt-1 and sKDR in patients undergoing CABG surgery with ECC.
- To understand the dynamics and potential functional implications of sFlt-1 release during this procedure.
Main Methods:
- Plasma samples collected from 15 patients before, during, and after CABG surgery.
- Quantification of sFlt-1 and sKDR levels using specific enzyme-linked immunosorbent assays (ELISA).
- Functional assays using human umbilical vein endothelial cells (HUVECs) to assess VEGF mitogenic response and flow cytometry to analyze cell shedding.
Main Results:
- A 75-fold increase in plasma sFlt-1 was observed during CABG surgery, returning to baseline by 6 hours post-operatively.
- Plasma sKDR levels remained unchanged throughout the surgical procedure.
- ECC-derived sFlt-1 demonstrated functional inhibitory effects on VEGF-induced endothelial cell proliferation, suggesting proteolysis rather than de novo synthesis.
- Vascular endothelial cells were identified as a potential source of ECC-induced sFlt-1.
Conclusions:
- sFlt-1 is actively released into circulation during CABG with ECC.
- The release of sFlt-1 may play a role in post-CABG complications by neutralizing VEGF and interfering with membrane-bound VEGF receptors.
- Further research is warranted to elucidate the precise mechanisms and clinical impact of sFlt-1 modulation in cardiac surgery.
Background:
This study was conducted to follow plasma concentrations of sFlt-1 and sKDR, two soluble forms of the vascular endothelial growth factor (VEGF) receptor in patients undergoing coronary artery bypass graft (CABG) surgery with extracorporeal circulation (ECC).
Methods:
Plasma samples were obtained before, during and after surgery in 15 patients scheduled to undergo CABG. Levels of sFlt-1 and KDR levels were investigated using specific ELISA.
Results:
A 75-fold increase of sFlt-1 was found during cardiac surgery, sFlt-1 levels returning to pre-operative values at the 6th post-operative hour. In contrast sKDR levels did not change during surgery. The ECC-derived sFlt-1 was functional as judge by its inhibitory effect on the VEGF mitogenic response in human umbilical vein endothelial cells (HUVECs). Kinetic experiments revealed sFlt-1 release immediately after the beginning of ECC suggesting a proteolysis of its membrane form (mFlt-1) rather than an elevated transcription/translation process. Flow cytometry analysis highlighted no effect of ECC on the shedding of mFlt-1 on platelets and leukocytes suggesting vascular endothelial cell as a putative cell source for the ECC-derived sFlt-1.
Conclusion:
sFlt-1 is released during CABG with ECC. It might be suggested that sFlt-1 production, by neutralizing VEGF and/or by inactivating membrane-bound Flt-1 and KDR receptors, might play a role in the occurrence of post-CABG complication.
