Gut microbiota-dependent phenylacetylglutamine in cardiovascular disease: current knowledge and new insights

Abstract

Phenylacetylglutamine (PAGln) is an amino acid derivate that comes from the amino acid phenylalanine. There are increasing studies showing that the level of PAGln is associated with the risk of different cardiovascular diseases. In this review, we discussed the metabolic pathway of PAGln production and the quantitative measurement methods of PAGln. We summarized the epidemiological evidence to show the role of PAGln in diagnostic and prognostic value in several cardiovascular diseases, such as heart failure, coronary heart disease/atherosclerosis, and cardiac arrhythmia. The underlying mechanism of PAGln is now considered to be related to the thrombotic potential of platelets via adrenergic receptors. Besides, other possible mechanisms such as inflammatory response and oxidative stress could also be induced by PAGln. Moreover, since PAGln is produced across different organs including the intestine, liver, and kidney, the cross-talk among multiple organs focused on the function of this uremic toxic metabolite. Finally, the prognostic value of PAGln compared to the classical biomarker was discussed and we also highlighted important gaps in knowledge and areas requiring future investigation of PAGln in cardiovascular diseases.

Keywords

PAGln / cardiovascular disease / gut microbiota / uremic metabolite / biomarker

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Acknowledgements

This work was supported by the National Key Research and Development Program of China (No. 2022YFC3400700), National Natural Science Foundation of China (Nos. 31971358, 82370397, U22A20266, and 82100402), Hubei Provincial Key Research and Developmental Program (No. 2022BCA037), and Hubei Provincial Natural Science Foundation of China (Nos. 2017CFB536 and 2022CFB201).

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Yaonan Song, Haoran Wei, Zhitong Zhou, Huiqing Wang, Weijian Hang, Junfang Wu, and Dao Wen Wang declare no conflicts of interest. This article does not involve a research protocol requiring approval by a relevant institutional review board or ethics committee.

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