Identification of proteomic alterations in TMAO‐Induced Cardiac Injury

Abstract

Gut microbial metabolite, trimethylamine N-oxide (TMAO), increases the risk of cardiovascular diseases. The present study was designed to determine the effects of TMAO on myocardial proteins in mice and to identify the molecular targets associated with the pathogenesis of TMAO-induced cardiac injury. C57BL/6J mice were treated with or without TMAO (120 mg/kg) for 4 weeks in drinking water. Using two-dimensional differential in-gel electrophoresis with 3 CyDye labeling and MALDI-TOF/TOF tandem mass spectrometry, we compared differences in the expression levels of proteins in the myocardium which were induced by chronic TMAO exposure. Proteomic analysis identified 31 protein spots with significant alterations in the myocardium of TMAO treated mice. Among these proteins, two members of the mitochondrial proteins (NDUFA9 and Cytochrome C oxidase subunit B) which are located in the inner mitochondrial membrane are found to be degraded in TMAO treated mice. In addition, TMAO treatment significantly enhanced mitochondrial reactive oxygen species (mtROS) production in the myocardium. In conclusion, our study indicate that chronic exposure to TMAO can cause extensive proteomic alterations in the myocardium, especially effecting the mitochondrial proteins responsible for complex I function of the electron transport chain (ETC) and eventually leading to cardiac injury.