Wei Shuai1, Jingyi Wen2, Xiuli Li3, Dan Wang4, Yunde Li5, Jian Xiang5. 1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. 2. Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. 3. From the (1)Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China. Electronic address: lixiuli791@163.com. 4. Department of Pathology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China. 5. From the (1)Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Abstract
BACKGROUND: Trimethylamine N-oxide, a gut microbe-dependent metabolite of dietary choline and other trimethylamine-containing nutrients, has been associated with a poor prognosis for patients with cardiovascular disease. However, the role and underlying mechanisms of trimethylamine N-oxide in the cardiac function of patients with heart failure with preserved ejection fraction (HFpEF) have not been elucidated. METHODS AND RESULTS: C57BL/6 mice were fed a normal diet, high-choline (1.2%) diet, and/or 3-dimethyl-1-butanol diet 3 weeks before the operation (uninephrectomy followed by a continuous saline or aldosterone infusion). Mice were assessed for 4 weeks after the operation. Echocardiographic and hemodynamic measurements were performed. Blood samples were evaluated for choline, trimethylamine N-oxide, and inflammatory factor levels. Left ventricular tissues were collected to assess myocardial fibrosis and inflammation. Left ventricular hypertrophy, pulmonary congestion, and diastolic dysfunction were markedly exacerbated in HFpEF mice fed high-choline diets compared with mice fed the control diet. Myocardial fibrosis and inflammation were markedly increased in HFpEF mice fed high-choline diets compared with animals fed the control diet. Additionally, 3,3-dimethyl-1-butanol DMB markedly ameliorated cardiac diastolic dysfunction, myocardial fibrosis and inflammation in the choline-fed HFpEF mice. CONCLUSIONS: A high-choline diet exacerbates cardiac dysfunction, myocardial fibrosis, and inflammation in HFpEF mice, and 3,3-dimethyl-1-butanol ameliorates the high-choline diet-induced cardiac remodeling.
BACKGROUND:Trimethylamine N-oxide, a gut microbe-dependent metabolite of dietary choline and other trimethylamine-containing nutrients, has been associated with a poor prognosis for patients with cardiovascular disease. However, the role and underlying mechanisms of trimethylamine N-oxide in the cardiac function of patients with heart failure with preserved ejection fraction (HFpEF) have not been elucidated. METHODS AND RESULTS: C57BL/6 mice were fed a normal diet, high-choline (1.2%) diet, and/or 3-dimethyl-1-butanol diet 3 weeks before the operation (uninephrectomy followed by a continuous saline or aldosterone infusion). Mice were assessed for 4 weeks after the operation. Echocardiographic and hemodynamic measurements were performed. Blood samples were evaluated for choline, trimethylamine N-oxide, and inflammatory factor levels. Left ventricular tissues were collected to assess myocardial fibrosis and inflammation. Left ventricular hypertrophy, pulmonary congestion, and diastolic dysfunction were markedly exacerbated in HFpEF mice fed high-choline diets compared with mice fed the control diet. Myocardial fibrosis and inflammation were markedly increased in HFpEF mice fed high-choline diets compared with animals fed the control diet. Additionally, 3,3-dimethyl-1-butanolDMB markedly ameliorated cardiac diastolic dysfunction, myocardial fibrosis and inflammation in the choline-fed HFpEF mice. CONCLUSIONS: A high-choline diet exacerbates cardiac dysfunction, myocardial fibrosis, and inflammation in HFpEF mice, and 3,3-dimethyl-1-butanol ameliorates the high-choline diet-induced cardiac remodeling.