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Trimethylamine/Trimethylamine-N-Oxide as a Key Between Diet and Cardiovascular Diseases

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Abstract

Trimethylamine (TMA) is a gut microbiota-derived metabolite which comes from diets rich of choline, betaine or l-carnitine and could be further converted to Trimethylamine-N-oxide (TMAO) in the liver. As the function of gut microbiota and its metabolites being explored so far, studies suggest that TMAO may be a potential risk factor of cardiovascular diseases independent of other traditional risk factors. However, the precise role of TMAO is controversial as some converse results were discovered. In recent studies, it is hypothesized that TMA may also participate in the progression of cardiovascular diseases and some cytotoxic effect of TMA has been discovered. Thus, exploring the relationship between TMA, TMAO and CVD may bring a novel insight into the diagnosis and therapy of cardiovascular diseases. In this review, we discussed the factors which influence the TMA/TMAO’s process of metabolism in the human body. We have also summarized the pathogenic effect of TMA/TMAO in cardiovascular diseases, as well as the limitation of some controversial discoveries.

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Abbreviations

TMA:

Trimethylamine

TMAO:

Trimethylamine-N-oxide

AS:

Atherosclerosis

DMB:

3, 3-Dimethyl-1butanol

NLRP3:

Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3

γBB:

γ-Butyrobetaine

PERK:

Protein kinase R-like endoplasmic reticulum kinase

SR-A:

Scavenger receptor-A

MAPK:

Mitogen-activated protein kinase

JNK:

C-JUN NH2-terminal protein kinase

NF-κB:

Nuclear factor kappa B

CD36:

Cluster of differentiation 36

HSP:

Heat shock protein

GRP:

Glucose-related protein

TXNIP:

Thioredoxin-interactive protein

ROS:

Reactive oxygen species

HMGB1:

High mobility group box 1

TNF-α:

Tumor necrosis factor α

IL-6:

Interleukin 6

VCAM-1:

Vascular cell adhesion molecule 1

PKC:

Protein kinase C

SIRT3:

Sirtuin 3

SOD2:

Superoxide dismutase 2

ERS:

Endoplasmic reticulum stress

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (Grant Nos. 82070299, 81870221, 81670249 and 31271226 to Dr. Wei Jiang)

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National Natural Science Foundation of China (Grant Nos. 82070299, 81870221, 81670249 and 31271226 to Dr. Wei Jiang).

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Authors and Affiliations

  1. West China School of Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China

    Siyu He & Hong Jiang

  2. The Laboratory of Cardiovascular Diseases, Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People’s Republic of China

    Caili Zhuo & Wei Jiang

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  1. Siyu He
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  2. Hong Jiang
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  3. Caili Zhuo
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  4. Wei Jiang
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SH was responsible for the collection and arrangement of articles associated with TMA/TMAO and cardiovascular diseases, manuscript writing and revision. HJ was responsible for figures drawing and part of the manuscript writing. CZ was responsible for the organization and revision of the manuscript. WJ made important intellectual contribution in research design, technical guidance and manuscript revision.

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Correspondence to Wei Jiang.

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He, S., Jiang, H., Zhuo, C. et al. Trimethylamine/Trimethylamine-N-Oxide as a Key Between Diet and Cardiovascular Diseases. Cardiovasc Toxicol 21, 593–604 (2021). https://doi.org/10.1007/s12012-021-09656-z

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