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Supp. Figure 1. Schema (normal rats). ・ Saline (control) ・ 11R-EGFP ・ 11R-HO-1. injection. sacrifice. 2 hrs. 6 hrs. 8 hrs. 24 hrs. 48 hrs. Day 0. Day 1. Day 2. ・ 2 hours (n=7). ・ 8 hours (n=7). Construct. Procedure. Sample size. Construct. Procedure. Sample size. 11R-HO-1.

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2 hrs.

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  1. Supp. Figure 1 Schema (normal rats) ・Saline (control) ・11R-EGFP ・11R-HO-1 injection sacrifice 2 hrs. 6 hrs. 8 hrs. 24 hrs. 48 hrs. Day 0 Day 1 Day 2 ・2 hours (n=7) ・8 hours (n=7) Construct Procedure Sample size Construct Procedure Sample size 11R-HO-1 Immunofluorescence 7 11R-HO-1 Immunofluorescence 7 ・24 hours (n=7) ・6 hours (n=42) Construct Procedure Sample size 11R-HO-1 Immunofluorescence 7(1) Construct Procedure Sample size Control Western blotting 7(2) ・48 hours (n=7) 7 Immunofluorescence, Diameter 7 11R-EGFP Diameter 11R-HO-1 Immunofluorescence, Diameter 7 Construct Procedure Sample size 7(1), 7 Western blotting (anti His, anti HO-1) 11R-HO-1 Immunofluorescence 7

  2. Supp. Figure 2. Single hemorrhage model A. Short time B. Long time ・Saline ・11R-EGFP ・11R-HO-1 Blood ・11R-HO-1 ・11R-HO-1 Blood injection injection injection injection injection 7 days 5 days 6 hrs. ② ① Sacrifice Sacrifice Day 0 Day 1 Day 2 Day 0 Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 A. B. ① 5 days (n=5) 6 hours (n=21) Construct Procedure Sample size Construct Procedure Sample size Control cGMP 7(2) 11R-HO-1 cGMP 5 11R-EGFP cGMP 7(1) 11R-HO-1 cGMP 7 ② 7 days (n=5) Construct Procedure Sample size 11R-HO-1 cGMP 5(1)

  3. Day 1 Day 1 Day 0 Day 0 Day 3 Day 3 Day 4 Day 4 Day 5 Day 5 Day 6 Day 6 Day 7 Day 7 Day 2 Day 2 ② 24 hours (n=14) ③ 8 hours (n=14) ① 48 hours (n=14) Construct Construct Construct Procedure Procedure Procedure Sample size Sample size Sample size 11R-EGFP 11R-EGFP 11R-EGFP Diameter Diameter Diameter 7(1) 7(1) 7(2) 11R-HO-1 11R-HO-1 11R-HO-1 Diameter Diameter Diameter 7(2) 7(1) 7 Construct Construct Procedure Procedure Sample size Sample size 11R-HO-1 11R-HO-1 Diameter, fluorescence Diameter, fluorescence 5(1) 5 Supp. Figure 3. Short time (A, B) ・Saline (control) ・HO-1 ・11R ・11R-EGFP ・11R –HO-1 Blood Blood 48 hrs. injection 24 hrs. 8 hrs. injection injection sacrifice B. 6 hrs. ① ② ③ ④ Long time (C) ・Blood ・Blood ・11R-HO-1 ・11R-HO-1 injection injection 7 days sacrifice 5 days ⑤ ⑥ A. ④ 6 hours (n=49) C. ⑤ 7 days (n=5) (the injection on day 0) Construct Procedure Sample size Control Diameter, fluorescence 7(2) HO-1 Diameter, fluorescence 7(1) 11R only Diameter, fluorescence 5 11R-EGFP Diameter, fluorescence 7(2) ⑥ 5 days (n=5) (the injection on day 2) 11R-HO-1 (0.15 mg/ml) Diameter, fluorescence 7(2) -2 Diameter, fluorescence 4 11R-HO-1 (5 x 10 mg/ml) -2 Diameter, fluorescence 4 11R-HO-1 (1.5 x 10 mg/ml) -3 Diameter, fluorescence 4 11R-HO-1 (1.5 x 10 mg/ml) -4 Diameter, fluorescence 4(1) 11R-HO-1 (1.5 x 10 mg/ml)

  4. Supp. Figure 4. Group Control HO-1 11R only 11R-EGFP 11R-HO-1 Variable (5 rats) (6 rats) (5 rats) (5 rats) (5 rats) blood pressure (mm Hg) 120 ± 12 124 ± 11 118 ± 10 121 ± 12 123 ± 13 PaCO2 (mm Hg) 46.4 ± 4.3 46.1 ± 5.4 44.5 ± 6.0 46.9 ± 5.2 45.8 ± 5.8 body temperature (℃) 37.5 ± 0.34 37.4 ± 0.24 37.5 ± 0.31 37.4 ± 0.19 37.2 ± 0.25 pH 7.40 ± 0.014 7.41 ± 0.027 7.40 ± 0.015 7.41 ± 0.017 7.42 ± 0.060

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