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ACE2

anti-sense. sense. a. b. c. 1.0. ACE. O kg/ml). 0.8. 0.6. ACE2. 0.4. Elastance (cmH 2. 0.2. WT. ace2 KO. 0.0. WT. ace2 KO. Supplementary Figure 1. c. a. *. Wet / dry ratio. WT, LPS. WT, saline. ace2 KO, saline. ace2 KO, LPS. 8. 7. 6. 5. 4. b.

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ACE2

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  1. anti-sense sense a b c 1.0 ACE O kg/ml) 0.8 0.6 ACE2 0.4 Elastance (cmH2 0.2 WT ace2 KO 0.0 WT ace2 KO Supplementary Figure 1

  2. c a * Wet / dry ratio WT, LPS WT, saline ace2 KO, saline ace2 KO, LPS 8 7 6 5 4 b ace2 KO, LPS+Zymosan WT, LPS+Zymosan 150 WT ace2 KO, saline WT, saline 100 % Changes in elastance 50 ace2 KO 0 0 1 2 3 hrs LPS Zymosan Supplementary Figure 2

  3. rhuACE2 2.5 Mut-rhuACE2 Mut-rhuACE2 rhuACE2 2.0 → 175KD 1.5 rhuACE2s Arbitary unit/hr → 83KD → 1.0 62KD Bovine IgG → 48KD 0.5 → 33KD 0 → 1 10 100 (ng/ml) 25KD 9 8 * 7 Wet / dry ratio 6 5 4 rhuACE2 rhuACE2 Mut-rhuACE2 Mut-rhuACE2 acid saline Wild type a b c Supplementary Figure 3

  4. * 4 600 6 600 3 400 AngII (fmol/ml) 4 Ang II (fmol/mg protein) 2 400 Ang II (fmol/mg protein) AngII (fmol/ml) * 200 1 2 200 0 ** ** ** ** 0 0 0 WT, acid ace2 KO, acid WT, control ace2 KO, control WT, acid WT, acid WT, acid ace-/-, acid ace2 KO, acid ace-/-, acid ace2 KO, acid WT, acid, rhuACE2 ace-/-ace2 KO, acid ace-/- ace2 KO, acid a b c d Supplementary Figure 4

  5. 7 * * 6 Wet /dry ratio 5 4 WT, acid WT, saline ace+/-, acid ace-/-, acid ace-/-, saline Supplementary Figure 5

  6. WT, LPS+Zymosan ace+/+ ace2 KO , LPS+Zymosan 150 ace-/- ace2 KO , LPS+Zymosan WT, saline ace-/- ace2 KO, saline 100 % Changes in elastance 50 0 0 1 2 3 hrs LPS Zymosan Supplementary Figure 6

  7. a b * 8 10 7 * Wet / dry ratio 8 Wet / dry ratio 6 * 6 5 4 4 WT, acid WT, saline agtr2-/y, acid agtr1a-/-, acid ace2 KO, saline, vehicle ace2 KO, acid, vehicle ace2 KO, saline, AT1R inhibitor ace2 KO, acid, AT1R inhibitor Supplementary Figure 7

  8. a b WT 12 WT 10 ace2 KO ace2 KO 10 8 8 Pperf (cmH2O) Pperf (cmH2O) 6 6 4 4 D D 2 2 0 0 Acid: + LPS: + + + AngI inj. AngII inj. AngI inj. AngII inj. Supplementary Figure 8

  9. 0.5 0.4 0.3 Fractional shortening acid 0.2 WT, acid 0.1 ace2 KO, acid 0 hrs 0 1 2 3 80 60 (mmHg) 40 Mean arterial pressure acid WT, acid 20 agtr1a-/-, acid 0 0 1 2 3 hrs a b 80 60 (mmHg) Mean arterial pressure 40 acid 20 WT, acid ace2 KO, acid 0 hrs 0 1 2 3 c Supplementary Figure 9

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