Figure 2. RAGE stimulation with HMGB1 triggers cardiomyocyte death via a β1AR-dependent mechanism.

(A) sRAGE abolished HMGB1-induced death of cultured adult rat cardiomyocytes. (B) HMGB1-induced myocyte death was abrogated by β1AR blockade with atenolol (0.3 μM) or CGP (0.3 μM), but not a β2AR blocker ICI (0.1 μM). In both panels, cultured adult rat cardiomyocytes were treated with HMGB1 (200 ng/ml) for 24 hours in the presence or absence of sRAGE or βAR blockers. (C) β1AR deficiency attenuated HMGB1- and ISO-induced death of adult mouse cardiomyocytes. Adult mouse cardiomyocytes were isolated from WT or β1AR KO mice. Cultured adult mouse cardiomyocytes were treated with HMGB1 (200 ng/ml) or ISO (1 μM) for 24 hours. Cell death was assayed by PI staining. Data were expressed as mean ± SEM for 4 independent experiments (at least 500 cells from 4 rats for each group). *P < 0.05; **P < 0.01; 1-way ANOVA. RAGE, receptor for advanced glycation end-products; HMGB1, high-mobility group box 1 protein; β1AR, β1-adrenergic receptor; sRAGE, soluble RAGE; CGP, CGP 20712A; ICI, ICI 118,551; ISO, isoproterenol; β1AR KO, β1-adrenergic receptor KO; PI, propidium iodide.