Courtney N. Zeller, Yue Wang, PhD, Troy A

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Presentation transcript:

Role of Tumor Necrosis Factor Receptor 1 in Sex Differences of Stem Cell Mediated Cardioprotection Courtney N. Zeller, Yue Wang, PhD, Troy A. Markel, MD, Brent Weil, MD, Aaron Abarbanell, MD, Jeremy L. Herrmann, MD, Megan L. Kelly, MS, Arthur Coffey, MD, Daniel R. Meldrum, MD The Annals of Thoracic Surgery Volume 87, Issue 3, Pages 812-819 (March 2009) DOI: 10.1016/j.athoracsur.2008.12.033 Copyright © 2009 The Society of Thoracic Surgeons Terms and Conditions

Fig 1 Intracoronary infusion of female MSCs provided greater cardioprotection compared with male MSCs. Although MSCs of either sex improved cardiac function after ischemic injury, hearts infused with FWT MSCs had greater functional recovery. This was seen in higher LVDP, +dp/dt, −dp/dt, and lower EDP during reperfusion (A, E, G) and at the end of reperfusion (D, F). No significant differences were noted when comparing EDP among all groups (C). (A, B, E–H): data were expressed as % of equilibration. (* = p < 0.05 MWT vs vehicle control; + = p < 0.05 FWT vs vehicle control; # = p < 0.05 FWT vs MWT as determined using two-way analysis of variance with repeated measures followed by a Bonferroni post hoc analysis (n = 5). (EDP = end diastolic pressure; FWT = female wild type; LVDP = left ventricular developed pressure; MSCs = mesenchymal stem cells; MWT = male wild type; • = vehicle control; ◯ = MWT; ◊ = FWT.) The Annals of Thoracic Surgery 2009 87, 812-819DOI: (10.1016/j.athoracsur.2008.12.033) Copyright © 2009 The Society of Thoracic Surgeons Terms and Conditions

Fig 2 Stem cells isolated from TNFR1 deficient male mice demonstrated greater degree of cardioprotection compared with their WT counterparts. Hearts infused with male TNFR1 knockout MSCs (MR1KO) demonstrated greater level of functional recovery compared with those infused with MWT MSCs (MR1KO). This was noted by higher LVDP, +dp/dt, −dp/dt, and lower EDP during reperfusion (A, C, E, G) and at the end of reperfusion (B, F, H). A statistically significant trend was observed when comparing the groups at the end of reperfusion (p = 0.1, D). (A, B, E–H): data were expressed as % of equilibration. (* = p < 0.05 MWT vs MR1KO as determined using two-way analysis of variance with repeated measures followed by a Bonferroni post hoc analysis [n = 5]; EDP = end diastolic pressure; LVDP = left ventricular developed pressure; MR1KO = male TNFR1KO; MSCs = mesenchymal stem cells; MWT = male wild type; TNFR1 = tumor necrosis factor receptor 1; • = MFWT; ◯ = MR1KO.) The Annals of Thoracic Surgery 2009 87, 812-819DOI: (10.1016/j.athoracsur.2008.12.033) Copyright © 2009 The Society of Thoracic Surgeons Terms and Conditions

Fig 3 No significant difference was observed in stem cell mediated cardioprotection between MSCs isolated from female TNFR1 deficient mice and their wild type counterparts. The MSCs isolated from TNFR1 knockout female mice did not demonstrate a greater level of cardioprotection compared with FWT MSCs after ischemia-reperfusion injury. No significant difference was observed in LVDP and EDP during reperfusion and at end reperfusion (A, B, C, D). Although +dp/dt and –dp/dt were significantly faster at 30 minutes after reperfusion (E, G), there is no difference in +dp/dt and –dp/dt at end reperfusion (F, H). (A, B, E–H): data were expressed as % of equilibration. (EDP = end diastolic pressure; FR1KO = female TNFR1KO; FWT = female wild type; LVDP = left ventricular developed pressure; MSCs = mesenchymal stem cells; TNFR1 = tumor necrosis factor receptor 1; * = p < 0.05 FWT vs FR1KO as determined using two-way analysis of variance with repeated measures followed by a Bonferroni post hoc analysis [n = 5]; • = FWT; ◯ = FR1KO.) The Annals of Thoracic Surgery 2009 87, 812-819DOI: (10.1016/j.athoracsur.2008.12.033) Copyright © 2009 The Society of Thoracic Surgeons Terms and Conditions

Fig 4 Intracoronary infusion of male MSCs isolated from TNFR1 deficient mice provided greater cardioprotection compared with FWT MSCs. The heart infused with male TNFR1 ablated MSCs (MR1KO) demonstrated higher LVDP, +dp/dt, −dp/dt, and lower EDP during reperfusion (A, C, E, G) and at the end of reperfusion (F). No significant differences were noted when comparing EDP at the end of reperfusion (D). (A, B, E–H): data were expressed as % of equilibration. (EDP = end diastolic pressure; MR1KO = male TNFR1KO; FWT = female wild type; LVDP = left ventricular developed pressure; MSCs = mesenchymal stem cells; TNFR1 = tumor necrosis factor receptor 1; * = p < 0.05 FWT vs MR1KO as determined using two-way analysis of variance with repeated measures followed by a Bonferroni post hoc analysis [n = 5]; • = FWT; ◯ = MR1KO.) The Annals of Thoracic Surgery 2009 87, 812-819DOI: (10.1016/j.athoracsur.2008.12.033) Copyright © 2009 The Society of Thoracic Surgeons Terms and Conditions