Figure 5. Inhibition of RAGE signaling with sRAGE or RAGE ablation blocks ISO-induced necrotic and apoptotic cell death.

(A) Deletion of RAGE diminished acute ISO treatment induced myocardial necrotic cell death, indexed by increased serum troponin I levels. Mouse serum was collected after 24-hour treatment of ISO (30 mg/kg, i.p.). Serum tropinin I was measured by ELISA (Abace-Biology). The averaged data were expressed as mean ± SEM from 4 mice for each group. **P < 0.01 as indicated; 1-way ANOVA. (B) Schematic presentation showing the experimental protocol for chronic ISO infusion in the presence or absence of cotreatment with daily sRAGE injection. (C and D) Treatment of mice with sRAGE prevents chronic ISO treatment–induced myocardial apoptotic cell death assessed by TUNEL-positive staining. Representative TUNEL staining (C) and the averaged data (D). Data were expressed as mean ± SEM from 10 mice of 3 independent experiments. **P < 0.01 versus vehicle; Student’s t test. Mice were subjected to chronic ISO treatment (60 mg/kg/d by minipump) in the presence or absence of sRAGE (8 ng/kg/d i.p.) for 7 days and then sacrificed for myocardial TUNEL staining. Scale bar: 20 μm. RAGE, receptor for advanced glycation end-products; sRAGE, soluble RAGE; ISO, isoproterenol; β1AR KO, β1-adrenergic receptor KO.