NAMPT-dependent NAD⁺ decline drives energy metabolism changes in aging-related atrial fibrillation.
11 affiliations
- 1Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, PR China.
- 2Modern Cardiovascular Disease Clinical Technology Research Center of Hunan Province, Changsha, Hunan, 410011, PR China.
- 3Cardiovascular Disease Research Center of Hunan Province, Changsha, Hunan, 410011, PR China.
- 4Research Institute of Blood Lipid and Atherosclerosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, PR China.
- 5Health Management Center, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
- 6Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
- 7International Medical Department, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. [email protected].
- 8Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, PR China. [email protected].
- 9Modern Cardiovascular Disease Clinical Technology Research Center of Hunan Province, Changsha, Hunan, 410011, PR China. [email protected].
- 10Cardiovascular Disease Research Center of Hunan Province, Changsha, Hunan, 410011, PR China. [email protected].
- 11Research Institute of Blood Lipid and Atherosclerosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, PR China. [email protected].
Abstract
Background
Atrial fibrillation (AF) is closely related to aging and involves energy metabolism remodeling. However, the changes in atrial energy metabolism associated with aging-related AF remain unclear.Methods
Left atrial appendage samples from AF patients were analyzed for nicotinamide adenine dinucleotide (NADtotal) levels using WST-8 method, adenosine triphosphate (ATP) content with an ATP detection kit, and silent information regulator sirtuin 1 (SIRT1) expression and protein acetylation levels via western blotting. Aged canine and mouse AF models were created through rapid atrial pacing and intravenous calcium chloride and acetylcholine administration, respectively. An aged cellular AF model was developed using electrical stimulation. Atria or cells from these models were analyzed for the aforementioned parameters. Co-immunoprecipitation in 293T cells verified the interaction between histone arginine methyltransferase 1 (CARM1) and circadian rhythm output cycle protein kaput (CLOCK), and rescue experiments with CARM1 and nicotinamide phosphoribosyl transferase (NAMPT) inhibitors explored their roles in regulating NAD⁺ and atrial energy metabolism remodeling in AF.Results
Clinical samples showed decreased NADtotal, SIRT1 and ATP levels, validated in aged canine, mouse, and cellular AF models. Cell-level tests revealed that the NAMPT activator P7C3-A20 increased NAD⁺ levels, while the inhibitor FK866 decreased them. Co-IP experiments indicated an interaction between CARM1 and CLOCK, with CARM1 expression upregulated in AF. Rescue experiments demonstrated that combined CARM1 and NAMPT inhibitors lowered NAD⁺ levels, suggesting that CARM1 regulates the CLOCK/NAMPT pathway, affecting NAD⁺ metabolism in AF.Conclusions
CARM1 may influence the CLOCK/NAMPT pathway and may be associated with reduced NADtotal evels, potentially contributing to impaired atrial energy metabolism in aging-related AF.
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BibTeX
@article{lin2026namptdependent,
title = {{NAMPT-dependent NAD⁺ decline drives energy metabolism changes in aging-related atrial fibrillation.}},
author = {Qiuzhen Lin and Chao Sun and Yunying Huang and Jiayi Zhu and Yingxu Ma and Yong Zhou and Keke Wu and Siyuan Tan and Yi Li and Tao Tu and Zhenjiang Liu and Fan Bai and Xiaobo Liao and Chan Liu and Qiming Liu},
journal = {BMC medicine},
year = {2026},
month = jul,
doi = {10.1186/s12916-026-05108-z},
url = {https://europepmc.org/article/MED/42972381},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - NAMPT-dependent NAD⁺ decline drives energy metabolism changes in aging-related atrial fibrillation.
AU - Qiuzhen Lin
AU - Chao Sun
AU - Yunying Huang
AU - Jiayi Zhu
AU - Yingxu Ma
AU - Yong Zhou
AU - Keke Wu
AU - Siyuan Tan
AU - Yi Li
AU - Tao Tu
AU - Zhenjiang Liu
AU - Fan Bai
AU - Xiaobo Liao
AU - Chan Liu
AU - Qiming Liu
PY - 2026
DA - 2026/07/31
JO - BMC medicine
DO - 10.1186/s12916-026-05108-z
UR - https://europepmc.org/article/MED/42972381
AB - Background Atrial fibrillation (AF) is closely related to aging and involves energy metabolism remodeling. However, the changes in atrial energy metabolism associated with aging-related AF remain unclear.Methods Left atrial appendage samples from AF patients were analyzed for nicotinamide adenine dinucleotide (NADtotal) levels using WST-8 method, adenosine triphosphate (ATP) content with an ATP detection kit, and silent information regulator sirtuin 1 (SIRT1) expression and protein acetylation levels via western blotting. Aged canine and mouse AF models were created through rapid atrial pacing and intravenous calcium chloride and acetylcholine administration, respectively. An aged cellular AF model was developed using electrical stimulation. Atria or cells from these models were analyzed for the aforementioned parameters. Co-immunoprecipitation in 293T cells verified the interaction between histone arginine methyltransferase 1 (CARM1) and circadian rhythm output cycle protein kaput (CLOCK), and rescue experiments with CARM1 and nicotinamide phosphoribosyl transferase (NAMPT) inhibitors explored their roles in regulating NAD⁺ and atrial energy metabolism remodeling in AF.Results Clinical samples showed decreased NADtotal, SIRT1 and ATP levels, validated in aged canine, mouse, and cellular AF models. Cell-level tests revealed that the NAMPT activator P7C3-A20 increased NAD⁺ levels, while the inhibitor FK866 decreased them. Co-IP experiments indicated an interaction between CARM1 and CLOCK, with CARM1 expression upregulated in AF. Rescue experiments demonstrated that combined CARM1 and NAMPT inhibitors lowered NAD⁺ levels, suggesting that CARM1 regulates the CLOCK/NAMPT pathway, affecting NAD⁺ metabolism in AF.Conclusions CARM1 may influence the CLOCK/NAMPT pathway and may be associated with reduced NADtotal evels, potentially contributing to impaired atrial energy metabolism in aging-related AF.
SN - 1741-7015
ER -