Identification of a new regulatory mechanism of cardiac calcium channels by Cereblon

Heart failure is the second leading cause of death in Korea after cancer, and is considered as a high-risk disease that increases in prevalence every year. Heart failure, which leads to decreased heart function, stems from different causes, but the exact pathogenic mechanism and treatment remain unknown, with most treatments targeting its early stages which includes hyperlipidemia and hypertension. Prof. Jin Han and Prof. Hyoung Kyu Kim's research team at Inje University recently conducted a multi-year research to reveal a novel function of Cereblon protein (CRBN) in the heart, which is known for its ability to selectively degrade Cav1.2α through the ubiquitin-proteasome-proteolytic complex, and to identify its association with heart failure with reduced ejection fraction (HFrEF).

The research team confirmed the increased expression of CRBN in the heart of patients with HFrEF, and based on this, created a mouse model that suppressed CRBN expression in the heart. Using this model, a new regulatory mechanism has been identified. In addition, for the first time in the world, the disease association of mice with reduced CRBN has better cardiac contractility and resistance to heart disease. The results of this study were published online in February 2022 in the European Heart Journal IF 29.9, the world's top journal for cardiovascular disease.

[Reference]  Park, Nammi, et al. "Cereblon contributes to cardiac dysfunction by degrading Cav1. 2α." European Heart Journal (2022).https://doi.org/10.1093/eurheartj/ehac072

[Main Author] Nammi Park, Jubert Marquez, Hyoung Kyu Kim, Jin Han (Inje University)

* Contact email : Prof. Hyoung Kyu Kim (estrus@inje.ac.kr), Prof. Jin Han (phyhanj@inje.ac.kr)

CRBN modulates cardiac function by altering Cav1.2α current density and a targeted approach of reducing CRBN levels could serve as a promising strategy for HFrEF therapeutics.