Trimethylamine N-oxide (TMAO) is closely related to cardiovascular diseases, particularly heart failure (HF). Recent studies shows that 3,3-dimethyl-1-butanol (DMB) can reduce plasma TMAO levels. However, the role of DMB in overload-induced HF is not well understood. In this research study, we explored the effects and the underlying mechanisms of DMB in overload-induced HF. Aortic banding (AB) surgery was performed in C57BL6/J mice to induce HF, and a subset group of mice underwent a sham operation. After surgery, the mice were fed with a normal diet and given water supplemented with or without 1% DMB for 6 weeks. Cardiac function, plasma TMAO level, cardiac hypertrophy and fibrosis, expression of inflammatory, electrophysiological studies and signaling pathway were analyzed at the sixth week after AB surgery. DMB reduced TMAO levels in overload-induced HF mice. Adverse cardiac structural remodeling, such as cardiac hypertrophy, fibrosis and inflammation, was elevated in overload-induced HF mice. Susceptibility to ventricular arrhythmia also significantly increased in overload-induced HF mice. However, these changes were prevented by DMB treatment. DMB attenuated all of these changes by reducing plasma TMAO levels, hence negatively inhibiting the p65 NF-κB signaling pathway and TGF-β1/Smad3 signaling pathway. DMB plays an important role in attenuating the development of cardiac structural remodeling and electrical remodeling in overload-induced HF mice. This may be attributed to the p65 NF-κB signaling pathway and TGF-β1/Smad3 signaling pathway inhibition.

三甲胺N-氧化物（TMAO）与心血管疾病，尤其是心力衰竭（HF）密切相关。最近的研究表明3,3-二甲基-1-丁醇（DMB）可以降低血浆TMAO水平。但是，DMB在超负荷诱导的HF中的作用尚不清楚。在这项研究中，我们探讨了DMB在超负荷诱导的HF中的作用及其潜在机制。在C57BL6 / J小鼠中进行了主动脉束带（AB）手术以诱导HF，并且对部分小鼠进行了假手术。手术后，给小鼠喂食正常饮食，并补充有或没有1％DMB的水，持续6周。在AB手术后第6周分析了心脏功能，血浆TMAO水平，心脏肥大和纤维化，炎症表达，电生理研究和信号通路。DMB降低了超负荷诱导的HF小鼠的TMAO水平。在超负荷诱导的HF小鼠中，不良的心脏结构重塑，例如心脏肥大，纤维化和炎症，都增加了。在超负荷诱导的HF小鼠中，对室性心律不齐的敏感性也显着增加。但是，DMB处理可防止这些变化。DMB通过降低血浆TMAO水平来减弱所有这些变化，从而负面抑制p65NF-κB信号通路和TGF-β1/ Smad3信号通路。DMB在减轻超负荷诱导的HF小鼠心脏结构重塑和电重塑的发展中起重要作用。这可能归因于p65NF-κB信号通路和TGF-β1/ Smad3信号通路抑制。纤维化和炎症在超负荷诱导的HF小鼠中升高。在超负荷诱导的HF小鼠中，对室性心律不齐的敏感性也显着增加。但是，DMB处理可防止这些变化。DMB通过降低血浆TMAO水平来减弱所有这些变化，从而负面抑制p65NF-κB信号通路和TGF-β1/ Smad3信号通路。DMB在减轻超负荷诱导的HF小鼠心脏结构重塑和电重塑的发展中起重要作用。这可能归因于p65NF-κB信号通路和TGF-β1/ Smad3信号通路抑制。纤维化和炎症在超负荷诱导的HF小鼠中升高。在超负荷诱导的HF小鼠中，对室性心律不齐的敏感性也显着增加。但是，DMB处理可防止这些变化。DMB通过降低血浆TMAO水平来减弱所有这些变化，从而负面抑制p65NF-κB信号通路和TGF-β1/ Smad3信号通路。DMB在减轻超负荷诱导的HF小鼠心脏结构重塑和电重塑的发展中起重要作用。这可能归因于p65NF-κB信号通路和TGF-β1/ Smad3信号通路抑制。DMB通过降低血浆TMAO水平来减弱所有这些变化，从而负面抑制p65NF-κB信号通路和TGF-β1/ Smad3信号通路。DMB在减轻超负荷诱导的HF小鼠心脏结构重塑和电重塑的发展中起重要作用。这可能归因于p65NF-κB信号通路和TGF-β1/ Smad3信号通路抑制。DMB通过降低血浆TMAO水平来减弱所有这些变化，从而负面抑制p65NF-κB信号通路和TGF-β1/ Smad3信号通路。DMB在减轻超负荷诱导的HF小鼠心脏结构重塑和电重塑的发展中起重要作用。这可能归因于p65NF-κB信号通路和TGF-β1/ Smad3信号通路抑制。