Atorvastatin, but not pravastatin, induced unresolved ER stress, inhibited Akt, and induced apoptosis in cardiac myocytes. NMVMs were incubated with either atorvastatin (Ator) or pravastatin (Prava) for 48 h. A) Immunoblot analysis of total cell lysates. B) Ator increased the expression of IRE-1α. C) Both statins increased the protein expression of PDI, indicative of ER stress. D) Ator reduced Akt survival signaling, whereas Prava increased the activation of AktS473. E) Prava increased the expression of ERK-1/2t202/Y204. F–I) Ator increased the expression of CHOP (F), cleaved poly(ADP-ribose) polymerase (G), and cleaved caspase-3 (H, I). B–I) Densitometric analysis of representative immunoblot bands (n = 3 wells/treatment, each experiment repeated 3 times). Means ± sem. **P < 0.01, ***P < 0.001, ****P < 0.0001 (1-way ANOVA with Tukey’s post hoc comparison).