Changes in cell autophagy and apoptosis during age-related left ventricular remodeling in mice and their potential mechanisms

Abstract

Cardiac structures and functions change with advanced age, but the underlying mechanisms are not well understood. Autophagy and apoptosis play important roles in the process of cardiac remodeling. This study was designed to explore changes in cell autophagy and apoptosis during age-related left ventricular remodeling and to determine whether the mitogen-activated protein kinase (MAPK) pathway is an underlying mechanism. Eight 5-month-old (adult group) and eight 24-month-old male C57bl/6 mice (aged group) were studied. The heart mass index, left ventricular mass index and hydroxyproline content of both groups were compared. Western Blotting was used to quantitate the protein expression of microtubule-associated protein 1 light chain 3 (LC3), Beclin-1, caspase-3, B-cell leukemia-2 (Bcl-2) and MAPKs in the left ventricles of adult and aged mice. Our results showed that the heart mass index, left ventricular mass index and hydroxyproline content in the left ventricles of the aged mice were increased significantly compared with the adult mice, indicating that left ventricular remodeling occurs with aging. The expression of LC3 and Beclin-1 in the left ventricles of aged mice were decreased significantly compared to adult mice. Meanwhile, the level of myocardial caspase-3 in adult mice remained the same in aged mice, and the level of myocardial Bcl-2 increased significantly in aged mice. There were no differences in the expression level of myocardial extracellular signal-regulated kinase 1/2 (ERK1/2), activated/phospho-ERK1/2, c-Jun N-terminal kinase 1/2 (JNK1/2) and p38 between aged and adult mice. However, the expression of myocardial activated/phospho-JNK1/2 increased significantly in aged mice, while activated/phospho-p38 decreased significantly. These findings indicate that autophagy decreases without a concurrent change in apoptosis during age-related left ventricular remodeling in mice. The MAPK pathway may be involved in the regulation of age-related left ventricular remodeling by modulating autophagy.