Circulating TMAO Levels Correlate with Coronary Plaque Vulnerability and Rupture

MedicalResearch.com Interview with:

Lemin Zheng, Ph.D.

Dr. Lemin Zheng

Lemin Zheng, Ph.D.
Professor, Lab Director, and Principal Investigator The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine
Peking University Health Science Center
Beijing  China

MedicalResearch.com: What is the background for this study?

Response: Optical coherence tomography (OCT) has been considered as an ideal tool to characterize accurately atherosclerotic plaques and has potential to detect plaque rupture due to high-resolution (10-20 μm) cross-sectional images of tissue with near infrared light (1-3). Trimethylamine-N-oxide (TMAO) is a gut microbiota-dependent-generated metabolite which is associated with cardiovascular risk by a pathway involving dietary ingestion of nutrients containing trimethylamine, including phosphatidylcholine, choline, and L-carnitine (4-6).

In the gut, choline, betaine and carnitine can be metabolized to trimethylamine (TMA) by gut flora microorganism. And TMA could be further oxidized to a proatherogenic species, TMAO, in the liver by flavin monooxygenases 3 (FMO3)4-6. These risk associations have been repeatedly shown in large observational trials (7-10).


MedicalResearch.com: What are the main findings?

Response: However, no one study has investigated the relationship between TMAO and atherosclerotic plaque and it remains unclear whether circulating TMAO level can predict the risk of vulnerable plaque. The present study demonstrated that plasma TMAO level was significantly higher in patients with plaque rupture compared to those with non-plaque rupture. Moreover, positive correlations between plasma TMAO level and lipid volume index were also observed. Circulating TMAO levels were correlated with the vulnerability and development of coronary plaque, and more especially plaque rupture. Therefore, our results suggest that TMAO may be a biomarker with relevance to coronary plaque vulnerability and progression.

MedicalResearch.com: What should readers take away from this report?

Response: TMAO affects the development of vulnerable plaque through many possible mechanisms include: TMAO promotes endothelial cell adhesion of leukocytes11. TMAO induces expression of cytokines and adhesion molecules through signaling of mitogen-activated protein kinase and nuclear factor-κB, and enhances macrophage levels of CD36 and formation of foam cells from macrophages5,11. TMAO participates in platelet hyper-reactivity and generation of a pro-thrombotic phenotype, which increases in vivo thrombosis risk12. Despite the numerous findings and mechanistic insights revealed regarding the impact of TMAO on various diseases, many questions still remain including: which gut microbiota formation of TMAO leads to atherosclerosis are not entirely clear5. It is also not known whether TMAO interacts directly with a specific receptor or whether it acts to alter signaling pathways indirectly by altering protein conformation (that is, via allosteric effects)5. The ‘‘chemical sensor’’ for TMAO within diverse cells remains unknown12. Discovery of a link between l-carnitine ingestion, gut microbiota metabolism and CVD risk has broad health-related implications.
Therefore such aspects can be deeply investigated for future research as a result of this study.

Citation:
Coronary Plaque Characterization Assessed by Optical Coherence Tomography and Plasma Trimethylamine-N-oxide Levels in Patients with Coronary Artery Disease
Fu, Qiang et al.
American Journal of Cardiology , Volume 0 , Issue 0
Qiang Fu, MD, PhD,Mingming Zhao, PhD,Dezhao Wang, MD, PhD,Hongyu Hu, MD,Caixia Guo, MD, PhD,Wei Chen, MD,Qun Li, MD, Lemin Zheng PhD ,
Buxing Chen MD, PhD

Qiang Fu and Mingming Zhao contributed equally to this work and should be considered co-first authors.
DOI: http://dx.doi.org/10.1016/j.amjcard.2016.07.071

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Last Updated on August 18, 2016 by Marie Benz MD FAAD