Reductions in gut microbiota‑derived metabolite trimethylamine N‑oxide in the circulation may ameliorate myocardial infarction‑induced heart failure in rats, possibly by inhibiting interleukin‑8 secretion

Li,Xiaoyan; Sun,Yongcun; Zhang,Xinru; Wang,Jing

doi:10.3892/mmr.2019.10297

Reductions in gut microbiota‑derived metabolite trimethylamine N‑oxide in the circulation may ameliorate myocardial infarction‑induced heart failure in rats, possibly by inhibiting interleukin‑8 secretion

Authors:
- Xiaoyan Li
- Yongcun Sun
- Xinru Zhang
- Jing Wang
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Affiliations: Department of Ultrasound, Jining No. 1 People's Hospital, Jining, Shandong 272000, P.R. China
Published online on: May 27, 2019 https://doi.org/10.3892/mmr.2019.10297
Pages: 779-786

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Abstract

Myocardial infarction (MI) is a common cause of chronic heart failure (HF). Increasing evidence has revealed that trimethylamine N‑oxide (TMAO), a gut‑microbiota‑derived metabolite, contributes to the pathogenesis of cardiovascular disease by promoting inflammation. Elevated levels of circulating TMAO have been reported in patients following MI and were associated with unfavorable outcomes. The present study examined whether reductions in circulating TMAO could attenuate the progression of HF in rats following MI. Sprague‑Dawley rats underwent coronary ligation to induce MI or a sham operation. Echocardiography confirmed MI and cardiac dysfunction one day following coronary ligation. MI and sham rats were then treated with either vehicle (tap water) or 1.0% 3,3‑dimethyl‑1‑butanol (DMB, a trimethylamine formation inhibitor) in tap water, for 8 weeks. At the end of the experiment, TMAO plasma levels were markedly elevated in vehicle‑treated MI rats compared with vehicle‑treated sham rats; however, TMAO plasma levels were reduced in DMB‑treated MI rats compared with vehicle‑treated MI rats. Both MI groups exhibited cardiac hypertrophy, lung congestion, left ventricular remodeling and impaired cardiac function, according to the results of anatomical analysis, echocardiography and left ventricular hemodynamics; however, these manifestations of MI‑induced HF were significantly improved in DMB‑treated MI rats compared with vehicle‑treated MI rats. The plasma levels of the chemokine interleukin (IL)‑8, and cardiac expression of IL‑8 and its receptors were significantly increased in vehicle‑treated MI rats compared with vehicle‑treated sham rats; however, these were normalized in DMB‑treated MI rats. In addition, elevated TMAO plasma level was positively correlated with increased IL‑8 plasma level in MI groups. Notably, DMB treatment of sham rats also reduced plasma TMAO, but did not alter other parameters. These results indicated that reducing circulating TMAO may ameliorate the development of chronic HF following MI in rats, potentially by inhibiting IL‑8 secretion. The results from the present study suggested that inhibition of TMAO synthesis may be considered as a novel therapeutic approach for the prevention and treatment of patients with chronic MI‑induced HF.

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