Trimethylamine N-Oxide and Smoking Are Associated With the Progression of Thromboangiitis Obliterans

Abstract

Introduction

Thromboangiitis obliterans (TAO) is potentially associated with smoking, although its precise pathogenesis remains unclear. Trimethylamine N-oxide (TMAO) has been implicated in the induction of various cardiovascular and cerebrovascular diseases. However, the role of TMAO in TAO has not been reported. This study aimed to investigate the relationship between smoking, TMAO, and TAO.

Materials and methods

Thirty-three patients diagnosed with TAO and hospitalized for treatment between January 2018 and July 2024 were included in the study. Healthy smokers (n = 38) and nonsmokers (n = 35) were randomly recruited and matched for age, sex, and education level as controls. Subsequently, we analyzed their clinical characteristics, levels of TMAO, and immune and inflammatory markers.

Results

Patients with TAO exhibited significantly higher levels of TMAO, Toll-like receptor 4 (TLR4), receptor for advanced glycation end products, interleukin (IL)-1β, IL-18, tumor necrosis factor-alpha, high mobility group box 1, nuclear factor-κB (NF-κB), and phosphorylated NF-κB (pNF-κB) than those in the smoking and nonsmoking control groups (all P < 0.05). The smoking control group also exhibited significantly higher levels of TMAO, TLR4, IL-1β, NF-κB, and pNF-κB (all P < 0.05) than the nonsmoking control group. TMAO, IL-1β, and tumor necrosis factor-alpha levels were significantly higher in the underage smoking group (all P < 0.05) than in the adult smoking group. The level of TMAO was significantly correlated with the Rutherford classification in patients with TAO, patients' smoking status (including total years of smoking and average daily cigarette consumption), and immune and inflammatory markers (all P < 0.05).

Conclusions

These findings indicate that gut microbiota plays a significant role in the pathogenesis of TAO. TMAO is likely involved in the pathogenesis and progression of TAO, with smoking acting as a contributing factor. The underlying mechanism may involve the activation of immune-inflammatory pathways, specifically the high mobility group box 1–receptor for advanced glycation end products/TLR4-NF-κB pathway.