Figure 3

Extracellular HSP27 exerts more profound proinflammatory and injurious effects on aging hearts through TLR4. Hearts isolated from TLR4-competent (WT) and TLR4-deficient (TLR4d) mice were perfused with recombinant HSP27 (1.0 or 2.0 µg/mL) for 30 min followed by 60 min washout. A) HSP27 dose-dependently depressed LVDP in both adult and aging WT hearts, but had a greater effect on aging hearts. Data are expressed as mean ± SE. n = 6 in each group; ^aP < 0.05 versus baseline (as 100%); ^bP < 0.05 versus dose-matched adult, ^cP < 0.05 versus age-matched hearts treated with a lower dose of HSP27. B) TLR4 deficiency essentially abolished the effect of HSP27 (2.0 µg/mL) on LVDP in both adult and aging hearts. Data are expressed as mean ± SE. n = 6 in each group; ^aP < 0.05 versus baseline (as 100%); ^bP < 0.05 versus time-matched adult WT. C) HSP27 dose-dependently upregulated myocardial production of cytokines in WT hearts, and aging WT hearts exhibited a greater response. TLR4 deficiency abolished the effect of HSP27 on myocardial cytokine production in both adult and aging hearts. Data are expressed as mean ± SE. n = 6 in each group; ^aP < 0.05 versus age/genotype-matched control; ^bP < 0.05 versus dose-matched adult, ^cP < 0.05 versus age-matched hearts treated with a lower dose of HSP27.