부산대학교 도서관

Introduction:Cardiovascular disease (CVD) risk is elevated in liver transplant (LT) patients. The underlying physiological mechanisms associated with LT related CVD are not yet fully understood. High levels of the gut microbiome metabolite trimethylamine N-oxide (TMAO) may contribute to an increased risk of atherosclerosis. The purpose of this study is to investigate if high circulating levels of TMAO contribute to vascular dysfunction in LT recipients.Hypothesis:We hypothesized that vascular dysfunction, including measures of conduit artery endothelial function, central systolic blood pressure and carotid intima media thickness (cIMT), would be correlated with higher TMAO levels.Methods:We enrolled 12 LT recipients (6 male; 6 female; Mean±SD: Age 58.75±8.45 yrs). Conduit artery endothelial function was measured via flow-mediated dilation with duplex ultrasound. Central aortic pressure waves were synthesized from radial artery waveforms acquired by applanation tonometry and the use of a generalized transfer function. Mean cIMT of the near and far wall was assessed via B mode ultrasound. Blood samples were analyzed for plasma TMAO by nuclear magnetic resonance spectroscopy.Results:As shown in Figure 1, conduit artery endothelial function (Mean±SD: 4.11±2.82%) was negatively associated with TMAO (10.94±9.65 μM; r= -0.87, p<0.001). There was no significant relationship between TMAO and central aortic pressure (131±17mmHg; r= 0.36, p=0.3) or cIMT (0.68±0.10mm; r= -0.08, p=0.8).Conclusions:Our results showed that LT recipients with higher levels of plasma TMAO had worse conduit artery endothelial function. Endothelial dysfunction is a well-established precursor to the development of atherosclerosis. Therefore, therapeutic strategies aimed at improving the health of the gut microbiome and subsequently reducing the levels of TMAO hold promise for preventing atherosclerosis in LT patients and should be investigated in future trials.