Upregulated LIMD1 alleviates pressure overload-induced cardiac hypertrophy via inhibits YAP1/AKT/GSK3β signaling
Year: 2025
Type: article
Abstract: 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.
Source: PLoS ONE
Authors: Fengwen Xie, Bin Yuan, Ye Zhang, Liru Chen, Yingmei Zhong, Quan Xu
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,382
OpenAlex ID: W4407402928