VCOM Research Day Program Book 2023

Graduate Student Research Biomedical

07 Chronic Treatment of Trimethylamine N-Oxide Undermines Mouse Cardiac Function and Structure

Hanzhang “Chris” Ding; Youjing Zheng; Jia-Qiang He Corresponding author email: hanzhangd@vt.edu

Graduate Program in Translational Biology, Medicine, and Health, Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine

Previous studies have established a connection between the human gut microbiota and cardiovascular diseases such as coronary atherosclerosis and heart failure. A disordered gut microbial composition can trigger systemic and local inflammation, which are known to be involved in the pathogenesis of cardiovascular diseases, especially atherosclerosis. One of the widely-studied gut microbiota-derived metabolites, trimethylamine N-oxide (TMAO), has been demonstrated as a major contributor in the development of cardiovascular diseases. In this present study, we aim to investigate the impact of chronic TMAO treatment on mouse cardiac function and structure and determine if males and females

are distinctively affected. Male and female C57BL/6 mice were fed with water containing 0.12% TMAO for 13 consecutive weeks while the control groups were provided with normal tap water. It was found that the left ventricle ejection fraction measured with echocardiography was significantly lower in both male and female TMAO-treated groups. Electrocardiogram (ECG) showed prolonged PQ and QRS intervals along with lower P and R wave amplitudes in TMAO groups. Furthermore, thickened left ventricle walls were observed in TMAO groups in the post-histological analysis. Together, our data suggests chronic exposure to TMAO impairs heart

function and structure in both male and female mice and eventually leads to cardiomyopathy and heart failure. Ongoing experiments include but are not limited to blood inflammatory cytokine [e.g., interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α)], immunohistological [e.g., cell infiltration and organic cation transporter (OCT)], qPCR and Western blot [e.g., OCT and sarco-endoplasmic reticulum calcium ATPase (SERCA)] analysis.

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