Figure 7
Wt-Hpx but not ms-HpxHM or ms-HpxRM decreased heme-induced stasis and increased HO-1, and was not protective when HO-1 was blocked by SnPP. (A) NY1DD mice were hydrodynamically infused with SB100X + wt-Hpx (n = 4), SB100X + ms-HpxHM (n = 3) or SB100X + ms-HpxRM (n = 4) plasmids. DSFCs were implanted 4 wks later and microvascular stasis was measured at 1 h and 4 h after infusion of heme (3.2 µmols/kg). Percentage of stasis (mean ± SD) was calculated at each time point. *p < 0.05 for wt-Hpx compared with ms-HpxHM and ms-HpxRM. P < 0.05 for comparison of wt-Hpx to ms-HpxHM or ms-HpxRM (B) Liver microsomes were immunostained for HO-1 (32 kDa). (C) HO activity was measured in liver microsomes 4 wks after NY1DD mice were hydrodynamically infused with LRS (n = 4), SB100X + Luc (n = 4), SB100X + wt-Hpx (n = 4), SB100X + ms-HpxHM (n = 3) or SB100X + ms-HpxRM (n = 4). P < 0.05 for comparison of wt-Hpx to LRS, Luc, ms-HpxHM or ms-HpxRM. (D) Treatment of NY1DD sickle mice overexpressing wt-Hpx with the HO inhibitor tin protoporphyrin (SnPP, 40 µmols/kg × 3 d, intraperitoneally) reversed the protection afforded by wt-Hpx. *P < 0.05 for comparison of wt-Hpx to wt-Hpx + SnPP. The wt-Hpx data (dashed line) in A and D were taken from Figure 4A.