Invasion of gut-derived escherichia coli extracellular vesicles exacerbates myocardial ischemia/reperfusion injury.

Myocardial ischemia-reperfusion injury in mice significantly enhanced the invasion of gut-derived bacterial extracellular vesicles into the heart.

• Rosa26.tdTomato reporter mice were colonized with E. coli expressing Cre recombinase to trace gut-derived EVs.
• FACS-beads and immunofluorescence techniques were used to detect bacterial EV invasion.
• Gut-derived bacterial EVs were found in cardiac tissue following myocardial ischemia-reperfusion injury.
• The translocation of EVs was significantly greater in ischemia-reperfusion injured mice compared to controls.

Bacterial extracellular vesicles were detected in peripheral blood of patients with ST-segment elevation myocardial infarction (STEMI) and correlated with LPS levels.

• The FACS-bead method was used to confirm the presence of bacterial EVs in peripheral blood of STEMI patients.
• There was a significant correlation between extracellular vesicles in peripheral blood and LPS levels in STEMI patients.
• The findings suggest that bacterial EVs can serve as key carriers for LPS translocation in this clinical setting.

Invading E. coli-derived extracellular vesicles exacerbated mobilization and infiltration of systemic and local inflammatory cells following myocardial ischemia-reperfusion injury.

• E. coli EVs amplified inflammatory responses both systemically and locally in cardiac tissue.
• Increased infiltration of inflammatory cells was observed in myocardial tissue following EV invasion.
• This inflammatory amplification contributed to aggravated myocardial damage and impaired cardiac function.

E. coli-derived extracellular vesicles aggravated myocardial damage and impaired cardiac function in the ischemia-reperfusion injury model.

• Myocardial damage was assessed in the context of gut-derived EV invasion following ischemia-reperfusion.
• Cardiac function was found to be impaired in association with increased E. coli EV invasion.
• The exacerbation of injury was attributed to the EV-driven amplification of inflammatory responses.

Glucagon-like peptide-2 (GLP-2) effectively alleviated inflammatory responses and myocardial injury by inhibiting the translocation of E. coli-derived extracellular vesicles.

• GLP-2 treatment reduced the translocation of gut-derived E. coli EVs into the systemic circulation and cardiac tissue.
• Inhibition of EV translocation by GLP-2 was associated with reduced inflammatory cell mobilization and infiltration.
• GLP-2 treatment resulted in attenuation of myocardial injury following ischemia-reperfusion.
• The findings provide a theoretical basis for the therapeutic potential of GLP-2 in cardiovascular diseases.

This study is described as the first to confirm the impact of gut-derived extracellular vesicles on myocardial ischemia-reperfusion injury.

• Prior studies had highlighted the gut microbiota-cardiovascular system relationship but the precise mechanisms remained incompletely understood.
• Bacterial EVs had been overlooked despite their potential roles in multiple pathological processes.
• The study reveals that E. coli EVs can amplify inflammatory responses in the context of myocardial ischemia-reperfusion injury.
• The findings provide new insights into the gut-heart axis.