Upregulated LIMD1 alleviates pressure overload-induced cardiac hypertrophy via inhibits YAP1/AKT/GSK3β signaling.

OBJECTIVES: Pathological cardiac hypertrophy plays a significant role in the development and progression of heart failure (HF). LIM Domain Containing 1 (LIMD1) serves as a crucial regulatory factor in protein-protein interactions during cellular signal transduction. This study aims to investigate the specific roles and mechanisms of LIMD1 in pathological cardiac remodeling.

METHODS: We employed an adeno-associated virus 9 (AAV9) system to overexpress LIMD1 in the hearts through tail vein injection. C57BL/6 mice underwent transverse aortic constriction (TAC) for four weeks. Cardiac function was assessed using echocardiography, while cardiac remodeling was evaluated through histopathology and molecular techniques.

RESULTS: Our findings demonstrated elevated levels of LIMD1 in murine hearts subjected to TAC treatment and H9c2 cells challenged with angiotensin II (Ang II). Compared with wild-type (WT) mice, those injected with AAV-9-LIMD1 exhibited significantly reduced TAC-induced cardiac dysfunction, hypertrophy, and fibrosis. Mechanistically, both in vitro and in vivo experiments suggested that the beneficial effects of LIMD1 might be associated with the inhibition of the YAP1/AKT/GSK3β signaling pathway.

CONCLUSION: In summary, this study is the first to demonstrate the protective effects of LIMD1 against TAC-induced pathological cardiac remodeling. These effects are attributed to the inhibition of the YAP1/AKT/GSK3β signaling pathway.