Therapeutic potentials of modulating autophagy in pathological cardiac hypertrophy

Cardiac hypertrophy is an adaptive response to increased overload, which is induced by various physiological or pathological stimuli. It is a common pathological process of a variety of cardiovascular diseases, which eventually leads to heart failure. The development of cardiac hypertrophy is accompanied by anomalous expression of genes such as autophagy-related (Atg) genes and abnormal activation of a series of signaling pathways. Autophagy, with a typical feature of double-membrane vesicle called the autophagosome, is a highly conserved lysosomal degradation process. Autophagosomes engulf cytoplasmic components and deliver them to lysosomes, which degrade cytoplasmic components such as damaged organelles, misfolded proteins to maintain cellular homeostasis and energy supply. Several lines of evidence suggested that autophagy as a double-edged sword was not only involved in physiological cardiac hypertrophy, but played a crucial role in pathological cardiac hypertrophy. However, the exact mechanism underlying the role of autophagy in regulating cardiac hypertrophy remains largely unknown. Here, we comprehensively characterize the dual effects of autophagy in promoting or inhibiting cardiac hypertrophy under a variety of physiological or pathological conditions. Moreover, we summarize the potential therapeutic effects of autophagic modulators on pathological cardiac hypertrophy. Finally, we discuss the advantages and challenges of autophagic modulators for the therapy of pathological cardiac hypertrophy.