Key result
AAV9-mediated LIMD1 overexpression reduces cardiac dysfunction and fibrosis in mice by inhibiting YAP1/AKT/GSK3β signaling.
Why the study?
Pathological cardiac hypertrophy significantly contributes to heart failure development, but the specific roles and mechanisms of LIMD1 in pathological cardiac remodeling remain unclear.
Overexpression of LIMD1 protects against pressure overload-induced pathological cardiac remodeling by inhibiting the YAP1/AKT/GSK3β signaling pathway.
LIMD1 overexpression attenuates murine TAC remodeling; hypothesis-generating for human pressure-overload therapies, needs translational validation.
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.
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Xie et al. (2025) studied Pathological cardiac hypertrophy. AAV9-mediated LIMD1 overexpression vs. Wild-type (WT) mice was evaluated on Cardiac dysfunction, hypertrophy, and fibrosis. AAV9-mediated overexpression of LIMD1 significantly reduced TAC-induced cardiac dysfunction, hypertrophy, and fibrosis in mice by inhibiting the YAP1/AKT/GSK3β signaling pathway.
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