The ubiquitin-proteasome system: A potential therapeutic target for heart failure

The rising incidence of heart failure (HF) is one of the biggest challenges in cardiovascular medicine. The persistent shortage of donor organs for transplantation has led to an expanding application of left ventricular assist devices as a bridge to recovery. Accumulating evidence suggests that the ubiquitin-proteasome system (UPS), which is responsible for protein degradation, plays a direct role in cardiac hypertrophy and HF and is impacted by mechanical unloading. The UPS system also plays a role in the cardiac regulation of apoptosis, cell mass, and sarcomere quality control. Furthermore, it is a key regulator of β₂-adrenergic signaling, cell excitability, and conductance. In this review, we discuss the roles of the UPS in cardiac health and disease, including its roles in the pathologic hypertrophy associated with HF and its reversal during mechanical unloading. Finally, we suggest future areas of research, including possible therapeutic strategies for reversing cardiac remodeling by targeting the UPS.