Effects of Phenylacetylglutamine on the Susceptibility of Atrial Fibrillation in Overpressure-Induced HF Mice

Abstract

Phenylacetylglutamine (PAGln), a gut metabolite is substantially elevated in heart failure (HF). The increase of PAGln in plasma is associated with atrial fibrillation (AF), and contributes to AF pathogenesis. However, the role of PAGln in AF with HF remains uncertain. Therefore, this study aimed to determine the effect of PAGln on AF after HF. Thoracic aortic coarctation (TAC) created overpressure-induced HF mice for 4 weeks. Histopathology, biochemical, echocardiographic for assessment of cardiac function, and electrophysiological examination of several electrophysiological indexes (ERP, SNRT, and the occurrence rate of AF) were performed at the end of the HF mice model. We found that plasma PAGln levels were significantly elevated in PAGln-treated HF mice and that PAGln aggravated maladaptive structural remodeling and electrical remodeling, which aggravated the vulnerability of AF, shortened the ERP duration, prolonged the SNRT, increased the occurrence rate of AF in HF mice. Mechanistically, PAGln exacerbated ROS accumulation and increased the levels of phosphorylated PLB and CAMK II. Overall, PAGln played a vital role in promoting the occurrence of AF in HF mice by activating the CAMK II signaling pathway.

Keywords:

• Phenylacetylglutamine
• CAMK II
• atrial fibrillation
• heart failure

Authors’ contributions

Hui Fu and Wei Shuai contributed equally to draft and review the manuscript. Bin Kong, Jun Zhu, Xi Wang, Yanhong Tang participated in data collection, analysis and interpretation. He Huang and Congxin Huang designed the study and supervised the project. All authors contributed to the article and approved the submitted version.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data that support the findings of this study, including the full set of images of raw immunoblot data and staining presented, is deposited in Mendeley Data, V1, doi: 10.17632/m35k5c9ftb.1.

Additional information

Funding

This work was supported by grants from the Technical Innovation Project of Hu Bei Province of China (Grant No. 2016ACA153) and the Fundamental Research Funds for the Central Universities (Grant No. 2042021kf0119).