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.
Cardiothoracic Surgery Department, Rabin Medical Center, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Yaron D
YD
Barac
Department of Cardiac Surgery, University of Leipzig Heart Center, Leipzig, Germany.
Fabian
F
Emrich
Cardiothoracic Surgery Department, Rabin Medical Center, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Efrat
E
Krutzwakd-Josefson
Transplant and Stem Cell Immunobiology Laboratory, Department of Surgery, University of California, San Francisco, San Francisco, California.
Sonja
S
Schrepfer
Department of Regenerative Medicine Research, Texas Heart Institute, Houston, Texas.
Luiz C
LC
Sampaio
Department of Regenerative Medicine Research, Texas Heart Institute, Houston, Texas.
James T
JT
Willerson
Texas Medical Center, Houston, Texas.
Robert C
RC
Robbins
The Technion Integrated Cancer Center, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel.
Aaron
A
Ciechanover
Department of Cardiac Surgery, University of Leipzig Heart Center, Leipzig, Germany.
Friedrich-Wilhelm
FW
Mohr
Cardiothoracic Surgery Department, Rabin Medical Center, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Dan
D
Aravot
Department of Regenerative Medicine Research, Texas Heart Institute, Houston, Texas. Electronic address: dtaylor@texasheart.org.
Doris A
DA
Taylor
D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D015398:Signal Transduction; D025801:Ubiquitin / Q000502:physiology*; D020257:Ventricular Remodeling
D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex
LVAD; autophagy; heart failure; proteosome; regenerative medicine