Abstract
Background
Cardiac hypertrophy is the common pathological process of multiple cardiovascular diseases. However, the molecular mechanisms of cardiac hypertrophy are unclear. Long non-coding RNA (lncRNA), a newly discovered type of transcript that has been demonstrated to function as crucial regulators in the development of cardiovascular diseases. This study revealed a novel regulatory pathway of lncRNA in cardiac hypertrophy.
Methods
The cardiac hypertrophy models were established by transverse aortic constriction (TAC) in mice and angiotensin II (Ang II) in HL-1 cardiomyocytes. Adeno-associated virus 9 (AAV9) in vivo and lncRNA Gm15834 and shRNA plasmids in vitro were used to overexpress and knock down lncRNA Gm15834. The myocardial tissue structure, cardiomyocyte area, cardiac function, protein expressions, and binding of lncRNA Gm15834 and Src-associated substrate during mitosis of 68 KDa (Sam68) were detected by hematoxylin and eosin (HE) staining, immunofluorescence staining, echocardiography, western blot and RNA immunoprecipitation (RIP), respectively.
Results
In cardiac hypertrophy models, inhibiting lncRNA Gm15834 could decrease Sam68 expression and nuclear factor kappa-B (NF-κB) mediated inflammatory activities in vivo and in vitro, but overexpressing lncRNA Gm15834 showed the opposite results. RIP experiments validated the binding activities between lncRNA Gm15834 and Sam68. Overexpression of Sam68 could counteract the anti-hypertrophy effects of lncRNA Gm15834 knockdown. Meanwhile, in vivo inhibition of lncRNA Gm15834 could inhibit Sam68 expression, reduce NF-κB mediated inflammatory activity and attenuate cardiac hypertrophy.
Conclusion
Our study revealed a novel regulatory axis of cardiac hypertrophy, which comprised lncRNA Gm15834/Sam68/NF-κB/inflammation, shedding a new light for identifying therapy target of cardiac hypertrophy in clinic.
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Data Availability
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
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Funding
This study was supported by Key Project of Natural Science Foundation of Heilongjiang Province of China (ZD2017015).
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Hongli Sun and Chao Song participated in the conception and design of the study. Material preparation, data collection and analysis were performed by Yongsheng Liu, Man Jiang, Meitian Zhang, Yawen Xie, Lixin Wang, Pilong Shi, Qianlong Zhang, Qianhui Zhang, Kai Liu and Jiajun Zhou. The first draft of the manuscript was written by Yongsheng Liu. All authors have commented on previous versions of the manuscript. All authors have read and approved the final draft.
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The present study was conducted according to the “Guide for the Care and Use of Laboratory Animals” (NIH publication, 8th Edition, 2011). All animal experiments involved in this subject were approved and agreed by the Ethics Committee of Harbin Medical University-Daqing.
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Liu, Y., Jiang, M., Zhang, M. et al. LncRNA Gm15834 Aggravates Cardiac Hypertrophy by Interacting with Sam68 and Activating NF-κB Mediated Inflammation. Cardiovasc Drugs Ther (2024). https://doi.org/10.1007/s10557-024-07569-x
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DOI: https://doi.org/10.1007/s10557-024-07569-x