Abstract
Rationale: Trimethylamine N-oxide (TMAO), a metabolite formed in the metabolism of dietary phosphatidylcholine, is elevated in the circulation of patients at increased risk for heart attack and adverse prognosis during heart failure. Objective: We investigated the effects of dietary choline and TMAO on the severity of heart failure following transverse aortic constriction (TAC). Methods and Results: Male C57Blk/6J mice were fed either control diet, a diet containing choline (1.2%) or a diet containing TMAO (0.12%) at 3 weeks prior to surgical TAC and were studied for 12 weeks. Left ventricular (LV) structure and function were monitored at 3 week intervals and myocardial tissue was collected at 12 weeks. Plasma TMAO levels were significantly (p < 0.01) increased in the choline (28.64 ± 2.30 μM) and TMAO (28.18 ± 4.27 μM) compared to the control group (1.87 ± 0.26 μM). Left ventricular ejection fraction (LVEF) was significantly (p < 0.05) worse in mice fed TMAO compared to control diet. LV end-diastolic and end-systolic diameters were significantly (p < 0.05) increased in the TMAO group compared to control diet. Myocardial fibrosis as measured with Picrosirius Red staining was also significantly greater (p < 0.01) in the TMAO and choline groups. Circulating BNP levels were significantly (p < 0.05) increased in the TMAO and choline groups. Conclusions: These data demonstrate that heart failure severity is significantly enhanced in mice fed diets containing either TMAO or choline. Our results suggest that consumption of food high in dietary nutrients that increase TMAO levels such as phosphatidylcholine may increase heart failure severity.
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