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Figure 4 Absence of OPN leads to lessened myocardial fibrosis after AngII infusion. Trichrome stained myocardial sections demonstrate fibrosis. Wild-type mice demonstrated a 10-fold increase in interstitial fibrosis (blue staining) in response to AngII (2.5 µg/kg/min) (0.7 ± 0.16% to 8.0 ± 1.37%; n = 12, p < 0.01) as compared to a more modest four-fold response in the OPN–/– (four-fold increase, 0.4 ± 2.4% to 1.6 ± 0.73%) mice whether infused with 2.5 µg/kg/min (n = 15) or 3 µg/kg/min AngII (n = 8), a dose that caused a greater absolute BP and change from baseline than that measured in the WT animals. (A) WT after three weeks of sham infusion; (B) WT after three weeks of AngII infusion at 2.5 µg/kg/min; (C) OPN–/– after three weeks of AngII infusion at 2.5 µg/kg/min; (D) OPN–/– after three weeks of AngII infusion at 3 µg/kg/min; (E) Quantitation of interstitial fibrosis, determined via analysis of digitized image of 20x magnified trichrome-stained section, expressed as percent of total myocardial cross-sectional area. Interstitial fibrosis was significantly increased in the treated WT group but was not increased in the treated OPN–/– groups (p < 0.001). No significant difference was detected between any of the sham-infused groups. White bars = control; hatched bars = AngII, 2.5 µg/kg/min; black bars = 3 µg/kg/min. Abbreviations as in Figure 1.