by Christina U. Lorentz, Norah G

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Journal of Molecular and Cellular Cardiology

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Factor XI contributes to myocardial ischemia-reperfusion injury in mice by Christina U. Lorentz, Norah G. Verbout, Zhiping Cao, Lijuan Liu, Monica T. Hinds, Owen J. T. McCarty, Ivan Ivanov, Erik I. Tucker, David Gailani, and András Gruber BloodAdv Volume 2(2):85-88 January 23, 2018 © 2018 by The American Society of Hematology

Effects of anti-FXI IgG 14E11 on FXII activation by FXIa and FXI autoactivation, in vitro. Effects of anti-FXI IgG 14E11 on FXII activation by FXIa and FXI autoactivation, in vitro. The 14E11 antibody binds the A2 domain of mammalian FXI and inhibits its activation by FXIIa. Experiments were performed to elucidate additional effects of 14E11 on the FXII-FXI axis. (A) FXIIa activity is shown as a function of 14E11 antibody concentration. A mixture of purified human FXII and FXIa was incubated with 14E11, and FXIIa amidolytic activity was measured and expressed as the concentration of FXIIa generated in the reaction mixture. The antibody inhibits activation of purified human FXII by purified human FXIa in a concentration-dependent manner, in vitro. (B) FXI autoactivation is shown as a function of 14E11 antibody concentration. Purified human FXI was mixed with purified leukocyte-derived DNA in the presence of various concentrations of 14E11. FXIa amidolytic activity was measured and expressed as the concentration of FXIa that was generated in the reaction mixture. The antibody inhibits the DNA-induced autoactivation of purified human FXI in a concentration-dependent manner, in vitro. Christina U. Lorentz et al. Blood Adv 2018;2:85-88 © 2018 by The American Society of Hematology

Effects of anti-FXI IgG 14E11 in the murine myocardial ischemia-reperfusion model. Effects of anti-FXI IgG 14E11 in the murine myocardial ischemia-reperfusion model. (A) Representative sections of mouse hearts from animals treated during ischemia with vehicle (top) or 14E11 (bottom), followed by 2-hour reperfusion. The images on the left show the AAR of ischemia as areas devoid of fluorescent microspheres, whereas the TTC-stained images at right show infarcted tissue (paler areas in which the TTC stain is not taken up). (B) AARs for each group were calculated and are presented as percentages of total ventricular volume. (C) Treatment with 14E11 reduced the infarct size (percentage of AAR undergoing infarction) after regional myocardial ischemia-reperfusion. Data are shown as the means ± SEM of infarct size normalized to the AAR (n = 10 mice/group; *P ≤ .0001, 14E11 vs vehicle). Christina U. Lorentz et al. Blood Adv 2018;2:85-88 © 2018 by The American Society of Hematology