Pravastatin slows the progression of heart failure by inhibiting the c-Jun N-terminal kinase-mediated intrinsic apoptotic signaling pathway.

Tumor necrosis factor‑α (TNF-α) and c‑Jun N‑terminal kinases (JNKs) are known to be associated with apoptosis and are important in cardiac remodeling. It remains to be determined whether statins inhibit cardiac remodeling through interfering with TNF‑α‑JNK‑related signaling pathways. This study was designed to investigate the effect of pravastatin on the progression of hypertrophy to heart failure in transverse aortic constriction (TAC) and the associations with TNF‑α‑JNK signaling. Either pravastatin (5 or 20 mg/kg/day) or vehicle was orally administered to male C57BL/6J mice with TAC. Cardiac remodeling and left ventricular hemodynamics, as well as JNK-dependent apoptotic signals were analyzed 4 weeks following TAC. Neonatal rat cardiomyocytes were cultured to investigate the effect of pravastatin on TNF‑α‑induced JNK‑related apoptotic signals. Notably, pravastatin reduced the heart/body weight and lung/body weight ratios. In addition, a decrease of left ventricular (LV) echocardiographic dimensions, an increase of LV fractional shortening and diastolic index, a reduction of JNK activity, caspase‑12 and Bax were observed in the pravastatin‑treated groups. The TNF‑α‑induced phosphorylation of JNK and upregulation of caspase‑12 and Bax in cultured cardiomyocytes was inhibited by pravastatin. These results indicated that pravastatin attenuates cardiac remodeling by inhibiting JNK‑dependent pro‑apoptotic signaling.