Cardiovascular diseases, such as Myocardial Infarction and stroke, are the number 1 cause of morbidity and mortality in our country, affecting more than 100.000 Italian people every year; with huge costs, both social and economic, for the families and the NHS.

The majority of heart attacks occur due to blood clotting (thrombus) that obstructs one or more coronary arteries (Coronary arteries supply oxygenated blood and nutrients to the heart muscle), but their inner workings have never been entirely clear.

For the very first time, a new Italian study proves that a gut microbiota, i.e. Escherichia Coli, is detectable in the circulation of patients with myocardial infarction and concentrates in coronary thrombi favoring thrombus growth. These data have been published on the European Heart Journal, the most prestigious journal of cardiology in the world.

The research has been carried out on a sample of 150 patients by a team of cardiologists, interventional cardiologists, anatomopathologists, clinical pathologists, and biologists, led by Francesco Violi Director of I Clinica Medica, Policlinico Universitario Umberto I in Rome.

The 50 patients with myocardial infarction showed a higher concentration of lipopolysaccharides, a constituent of bacterium membrane, in coronary thrombi versus the peripheral blood of patients with stable angina and in controls (50 with stable angina and 50 in controls). Molecular analysis revealed that Escherichia Coli was detectable in the peripheral circulation of   >30% of patients with myocardial infarction compared to 10% of patients with stable angina; conversely, Escherichia Coli was undetectable in controls. Due to the intestinal origin of Escherichia Coli, the scientists analysed if changes of gut permeability could contribute to this finding and demonstrated that an enhanced gut permeability was a potential mechanism accounting for the presence of Escherichia Coli in the peripheral circulation of patients with myocardial infarction.

The researchers also found an increased experimental thrombus growth, an effect blunted by co-administration of Toll-like receptor 4 inhibitor, suggesting that Escherichia Coli exerts a pro-thrombotic activity via interaction with Toll-like receptor 4.

“These results – says Francesco Violi – provide new insights into the mechanism of myocardial infarction and create new therapeutic possibilities thanks to the inhibitor of Toll-like receptor 4 or a plausible, future vaccine against Escherichia Coli."

References:

Low-grade endotoxaemia enhances artery thrombus growth via Toll-like receptor 4: implication for myocardial infarction - Roberto Carnevale, Sebastiano Sciarretta, Valentina Valenti, Flavio di Nonno, Camilla Calvieri, Cristina Nocella, Giacomo Frati, Maurizio Forte, Giulia d’Amati, Maria G Pignataro, Anna Severino, Roberto Cangemi, Alessio Arrivi, Marcello Dominici, Enrico Mangieri, Carlo Gaudio, Gaetano Tanzilli, Francesco Violi - European Heart Journal (2020), DOI https://doi.org/10.1093/eurheartj/ehz893

Further Information

Francesco Violi
Department of Clinical, Internal Medicine, Anesthesiology and Cardiovascular Sciences
francesco.violi@uniroma1.it