Augmented Survival, Angiogenic Properties and Mobilization of Human Endothelial Progenitor Cells Following Exposure to Sevoflurane

Abstract

Anesthetic preconditioning (APC) with volatile agents has cardiac anti‐ischemic virtues that may be linked to stimulating effects of volatile anesthetics on stem cells biology. We investigated the influence of sevoflurane (Sevo) on apoptosis, proliferation, incorporation in tube‐like structure and mobilization of human endothelial progenitor cells (EPCs). 7‐days old cultured EPCs derived from human cord blood mononuclear cells were exposed in vitro to sevoflurane 2% or 4% in air/5% CO2, or only to air/5% CO2 (sham control) for 2 hrs in a modular chamber. Proliferation, apoptosis and incorporation of EPCs into tube‐like structures of HUVEC was evaluated 24 hrs later. EPCs plasma levels were evaluated by flow‐cytometry and in vitro culture assay before exposure to sevoflurane (1 MAC in 50% O2) or only to 50% O2 (sham control) and 24 hrs afterwards, in blood samples collected from coronary artery disease patients. Values are expressed as means ± SEM, compared by ANOVA. In the in vitro preconditioning setting, sevoflurane stimulated EPCs proliferation estimated by the MTS assay (n = 12, p < 0.01 for 2% Sevo, p < 0.001 for 4% Sevo) and by counting adherent DilAcLDL+/ FITC‐UEAI+ cells (n = 4, p < 0.01 for 2% Sevo, p < 0.001 for 4% Sevo), diminished apoptosis measured by annexin V/ propidium iodide assay (n = 5, p < 0.05 for both 2% and 4% Sevo), and raised the number of incorporated DiIAcLDL‐EPCs into HUVEC tube‐like structures (n = 4, p < 0.01 for 2% Sevo, p < 0.001 for 4% Sevo) when compared to control. Plasma CD45dim/CD34+/CD309+ and CD45dim/CD34+/CD309+/CD133+ mononuclear cell populations were increased in Sevo treated patients (n = 15) vs. the control group (n = 10) at 24 h post‐exposure vs. baseline (p < 0.01), and the number of adherent DilAcLDL+/FITC‐UEAI+ cells in 7 days old EPCs cultures was significantly higher in the study group vs. control between the same time points (p < 0.05). Our data prove that sevoflurane positively influences the biology of EPCs both in vivo and vitro, and may have an important cardioprotective impact in various interventional and surgical heart procedures by improving angiogenesis and ischemic tissue repair.Support or Funding InformationThe financial support was provided by UEFISCDI Romania, research grant PN‐II‐RUTE‐2012‐3‐0463.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.