Effect of intestinal-derived trimethylamine oxide levels on prognosis of ischemic heart failure rats
ZHANG Xin1, SHI Rui1, NI Jianmei1, LIU Xiaowei1, GUO Qiong1, WANG Tao1, WANG Xiaojing1, CHEN Shaobo1
1. Department of Prevention and Therapy of Cardiovascular Diseases in Alpine Environment of Plateau in Characteristics Medical Center of Chinese People’s Armed Police Force/Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Tianjin 300162,China; 2. Nankai Hospital of ITCWM, Tianjin 300199, China
Abstract：Objective To evaluate the effect of trimethylamine oxide (TMAO) on the prognosis of ischemic heart failure rats. Methods SD rats were randomly divided into normal control group, sham group, model group (HF) and intervention group (HF-DMB). Rats in HF and HF-DMB groups underwent myocardial infarction simulation via ligation, and cardiac function was assessed at 4 weeks (4 W), 8 weeks (8 W) and 12 weeks (12 W) after surgery, respectively . The levels of Serum TMAO, BNP, CRP, LPS and IL-6 were detected, along with histological examination of myocardial tissue using HE and Masson staining. Fecal samples were also collected for 16S rDNA high-throughput sequencing analysis. Results Compared with Control group, HF group exhibited a significant decline in (LVEF) over time, the difference was most pronounced in the eighth week(27.68±6.41)%,also with a notable increase in circulating TMAO [(9534.02±202.75)nmol/L, (12713.06±243. 66)nmol/L, (4970.95±168.15) nmol/L], BNP[(37.26±3.41)ng/L, (59.17±3.80)ng/L, (58.83±4.41)ng/L], CRP[(179.30±13.85) μg/L, (186.40±13.47) μg/L, (187.21±11.35) μg/L], LPS[(92. 45±8.83)ng/L, (90.65±7.5) ng/L, (95.20±4.68) ng/L], IL-6[(97.57±3.48) pg/ml, (102.60±4.96) pg/ml, (107.70±4.70) pg/ml], levels compared with the control group (P<0.05). Myocardial pathological staining showed that more myocardial cells survived and the degree of fibrosis was reduced in HF-DMB group than in HF group. Sequencing analysis revealed increased microbial richness in the HF-DMB group compared with the HF group with increased Firmicutes and decreased Bacteroidetes at 8 weeks, resulting in a lowered Firmicutes/Bacteroidetes ratio. However, these changes were reversed in the HF-DMB-8W group. Conclusions Changes of circulating TMAO in ischemic heart failure rats are consistent with traditional heart failure evaluation markers. Specific inhibition of circulating TMAO can improve various indexes of heart failure, indicating its potential clinical value in heart failure treatment and prognostic assessment.
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2024, Vol. 35 
